Nancy A. Melville

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.

Among diagnostic interventions recommended to manage the common CAR-T cell therapy–associated side effect of immune effector cell–associated neurotoxicity syndrome (ICANS), only electroencephalogram (EEG) shows significant therapeutic benefit — while magnetic resonance imaging (MRI) and lumbar puncture appear to have limited value, new research shows.

“Our results emphasize for the first time the role of EEG in the current guidelines [for ICANS] but question the need for systematic MRI and lumbar puncture,” reported the authors of the study, published in Blood Advances.

The study underscores that “EEG does more that depict insignificant anomalies and plays a key role in patient management in daily practice,” first author Mattéo Mauget, said in an interview. He is a resident in the intensive care unit at the University Hospital of Rennes in France.

ICANS is among the most common of acute neurotoxicities occurring after CAR T-cell therapy, and international guidelines recommend MRI, lumbar puncture, and EEG in the management of the toxicity, which is typically treated with anti-cytokine therapy and steroids.

However, the guidelines widely vary. All recommend the use of MRI for ICANS grade 3 or higher, but fewer recommend the approach for grade 2. Meanwhile, only some recommend the use of lumbar puncture, and even fewer guidelines recommend the use of EEG.

While these measures are expensive — and in the case of lumbar puncture, invasive and burdensome for patients — the recommendations on these measures “rely on empirical practices and are only based on expert opinions with low scientific evidence,” the authors wrote.

To evaluate the interventions in a cohort of real-life patients treated with CAR T-cell therapy, the authors identified 190 consecutive patients receiving the therapy at the University Hospital of Rennes, France, between August 2018 and January 2023.

Of the patients, 62% were male and their median age was 64. Overall, 91 (48%) developed ICANS.

The majority of patients (73%) received CAR-T cell therapy for a refractory/relapsed (R/R) DLBCL (73%), and most (60%) had received the CAR-T product axicabtagene-ciloleucel (axi-cel) after two or more prior therapies.

While MRI was performed in 78% of patients with ICANS, the measure was determined to have had a therapeutic impact in just 4% of patients, despite common observations of abnormal findings.

Lumbar puncture was meanwhile performed in 47% of patients, resulting in preemptive antimicrobial agents in 7% of patients, with no infection detected.

While systematic EEG was performed in 56% of patients, the intervention led to therapeutic modifications among 16% of those patients.

“Our findings highlight some divergences between guidelines and daily practice regarding diagnostic investigations,” the authors noted.

The study “shows that EEG is the diagnostic investigation with the greatest therapeutic impact, while MRI and lumbar puncture appear to have a limited therapeutic impact,” they concluded.
 

EEG Findings

Of note, only 18% of EEGs in the cohort were normal, ranging from 50% of those with ICANS grade 1 to 6% among those with ICANS grade 4.

Encephalopathy was the most common EEG finding, observed in 45% of patients, while 6 EEGs (12%) showed seizures or status epilepticus.

Two patients with ICANS grade 2 and 3 (6% of EEG) developed seizure or status epilepticus on their EEGs, despite the absence of clinical symptoms of epilepsy, while the rate was 4 (33%) among patients with ICANS grade 4.

Among the eight (16%) patients who received therapeutic modification as the result of the EEG, seven were in the severe and life-threatening ICANS (grade 3+) group (24%).

In addition, all EEGs detecting seizure or status epilepticus resulted in an increase in antiepileptic prophylaxis with levetiracetam or the introduction of a new antiepileptics, mainly phenytoin.

Surprisingly, there were no cases of diffuse edema in the entire cohort, even among those with grade 4 ICANS, which is one of the key concerns of treating physicians managing severe ICANS, the authors noted.

A notable caveat is that EEG can be a time- and physician-consuming examination not easily accessed on a 24/7 daily practice level.

With such challenges, “[we] advocate for a close partnership between hematologists and electrophysiologists to make EEG access as easy as possible for this kind of patient, as EEG is a key game changer in patient course,” Mr. Mauget said.

Commenting on the findings, Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program at the Massachusetts General Hospital Cancer Center in Boston, agreed that the study adds importantly to a topic in need of more data.

“This is a very interesting study that starts to provide data behind the consensus recommendations that were initially made based purely on expert opinion and collective practices,” she said in an interview.

“I think [the EEG findings] are interesting, because EEG is often the most non-specific of these tests, and I would not have predicted this result. I also think that monitoring of cerebral spinal fluid [through lumbar puncture] could have potentially higher impact if there was a way to routinely quantify and detect the CAR-T cells,” Dr. Maus said.

“Although admittedly I think this may be of greater benefit when patients present with neurologic findings outside the typical window of ICANS, such as what can occur with delayed neurologic toxicities such as Parkinsonism after BCMA-directed CAR T cells,” she added.

Senior author Guillaume Manson, MD, a hematologist also with the University Hospital of Rennes, underscored that the results shouldn’t be construed to suggest that MRI or LP should not be used in such cases, but may often not be necessary.

“Every patient’s case is different, and these findings certainly do not say that certain tests should or should not be performed,” he said in a press statement.

“We did this research to generate clinical evidence to inform guidelines that support physicians in making clinical decisions when treating patients with these complex, and sometimes severe conditions,” he added.

Dr. Manson reported relationships with BMS-Celgene, Gilead-Kite, and Takeda. Dr. Maus disclosed ties with Century Therapeutics, TCR2, Kite/Gilead, Novartis, and several other companies in the field of cellular therapies.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Among adolescents with moderate to severe obesity, a nutritionally balanced, very low-calorie diet with the monitoring of a dietitian shows high adherence and safety, with significant weight loss over the course of a month and common, but mild side effects.

More research is needed to understand which patients are best suited for the diet; “however, given the associated rapid weight loss, the use of [very low-energy diets] should be emphasized in clinical practice guidelines for the treatment of severe obesity and obesity-related complications in adolescents, especially before pharmacological or surgical intervention,” first author Megan Gow, PhD, of Children’s Hospital Westmead Clinical School, The University of Sydney, Westmead, Australia, said in a press statement. 

The study will be presented in May at the upcoming European Congress on Obesity, in Venice, Italy.

While very low-calorie diets have been shown to promote rapid weight loss in adolescents, research is lacking on general side effects and acceptability of the regimens. Data is also lacking on important issues including the diet’s effect on growth, heart health, and psychological wellbeing. 

To investigate, Dr. Gow and colleagues conducted a subanalysis of the 52-week Fast Track to Health study evaluating the acceptability of different dietary plans for adolescents with obesity.

The analysis included 141 adolescents between the ages of 13 and 17 years with moderate to severe obesity (average body mass index, 35 kg/m²) and at least one obesity-related complication, such as high blood pressure or insulin resistance.

The participants were placed on a nutritionally balanced very low-energy diet consisting of 800 calories per day. 

The diet involved one of two regimens — either four Optifast-formulated meal replacement products per day, including shakes, soups, bars, and/or dessert, along with low carbohydrate vegetables, such as broccoli, celery, capsicum, mushrooms, and tomatoes, with one teaspoon of vegetable oil, or a regimen of three Optifast-formulated meal replacements and one meal consisting of 100-150 g lean cooked meat, low-carbohydrate vegetables, and one teaspoon of vegetable oil.

Participants, about half of whom were women, also received dietitian support at least weekly. 

After 4 weeks, most of the adolescents, ie, 134 of the 141, with an average age of 14.9 years, completed the diet, with an average weight loss of 5.5 kg or 12 pounds (P < .001).

Most patients (95%) experienced at least one side effect, and 70% reported at least 3 of the side effects, with the most common side effects including hunger, fatigue, headache, irritability, loose stools, constipation, nausea, and a lack of concentration.

Viral infections occurred in seven participants.

While most side effects occurred at the end of week 1, the development of side effects earlier, at day 3-4, was associated with higher levels of weight loss at the 4-week cut-off, which the authors noted could suggest a greater adherence to the diet at that stage.

One adverse event occurred, consisting of a single fainting episode determined to be potentially related to the dietary intervention.

In surveys, the adolescents gave the intervention an acceptability rating of 61 on a scale of 100, the score was 53 of 100 in terms of being “enjoyable to follow.”

The most-liked aspects of the intervention were losing weight (described by 34% of participants) and the prescriptive structure (listed by 28% of participants).

The least-liked aspects included the diet’s restrictive nature, described by 45% of participants, and the taste of meal replacement products, listed by 20% of participants.
 

Alternative to Weight Loss Drugs?

While weight loss drugs are transforming the obesity treatment and semaglutide is now approved for adolescents as young as age 12 years, “access to these medications is limited, and not all families want to commence on medication for their child›s obesity,” Dr. Gow said.

As an alternative, a very low-energy diet, with the interaction of a dietitian, can enable adolescents “to develop a healthier relationship with food, including encouraging the consumption of more fruits and vegetables in their diet, not only to assist in weight loss but for good health,” she said.
 

Very Low-Calorie Diet Concerns for Adolescents Addressed

Early studies suggested concerns of health effects from very low-calorie diets in adolescents, including potential cardiac effects; however, subsequent studies, including a systematic review published by Dr. Gow and her team, have shown that such results were likely the result of nutritional deficiencies in the diets, which can be overcome with careful food selection and dietary counseling.

Another key concern has been a potential effect on growth, but Dr. Gow noted that “in our short-term study we saw small increase in height (0.1 cm), and other more recent studies suggest that a short-term very low-energy diet does not impact growth.”

And in an earlier pilot study, the authors also found an association between the very low-calorie diet and an improvement in the quality of life for youth with type 2 diabetes.

A key caveat with the findings is that participants in the study all received supervision and monitoring from a trained dietitian, and Gow noted that that element is essential.

“We therefore do not recommend adolescents in the community undertake this type of diet without appropriate support,” she said.

“Close monitoring of adolescents by a health professional following a very low-energy diet is essential to ensure that the very low-energy diet is leading to holistic health benefits for the individual.”

Following the 4-week regimen, participants were randomized to transition to interventions of either continuous energy restriction or intermittent energy restriction over the 52 weeks, and further findings from the study will be presented at the obesity meeting in May.

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE: 

The spices and aromatic herbs of the Mediterranean diet with significant benefits in improving glycemic health in type 2 diabetes are limited to ginger, cinnamon, black cumin, turmeric, and saffron, with ginger, black cumin, and cinnamon having the strongest effects on fasting glucose, according to a systematic review and meta-analysis of research.

The meta-analysis also evaluated clove, thyme, turmeric, and various other spices and herbs common in the diet but showed no other correlations with glycemic benefits. 

METHODOLOGY:

• In the analysis of 77 studies, 45, involving 3050 participants, were included in the meta-analysis and 32 studies in the systematic review.
• The studies’ inclusion criteria included adult patients with type 2 diabetes, with data on fasting glucose and/or A1c and/or , and involving any supplementation with black cumin, clove, , saffron, thyme, ginger, black pepper, , curcumin, cinnamon, basil, and/or oregano.
• The number of studies involving clove, parsley, thyme, black pepper, rosemary, basil, or oregano and their association with glycemic factors in people with type 2 diabetes was insufficient, hence the analysis primarily focused on the remaining five ingredients of cinnamon, curcumin, ginger, black cumin, saffron, and rosemary.

TAKEAWAY: 

• Improvements in fasting glucose of subjects with type 2 diabetes were observed with all five ingredients of cinnamon, turmeric, ginger, black cumin, and saffron.
• However, the most significant decreases in fasting glucose, between 17 mg/dL and 27 mg/dL, occurred after supplementation with black cumin, followed by cinnamon and ginger.
• Notably, only ginger and black cumin were associated with a significant improvement in A1c.
• Only cinnamon and ginger were associated with a significant decrease in insulin values.
• Of the 11 studies including cinnamon in the meta-analysis, 6 reported significant differences in fasting glucose, while 4 had differences in A1c after the supplementation.
• However, ginger was the only component associated with a significant decrease in each of the 3 outcomes examined of fasting glucose, A1c, and insulin.

IN PRACTICE:

“The Mediterranean Diet is the dietary pattern par excellence for managing and preventing metabolic diseases, such as type 2 diabetes,” the authors reported.

“As far as we are aware, this is the first systematic review and meta-analysis aiming to evaluate the effect of aromatic herbs and spices included in the Mediterranean Diet, such as black cumin, clove [and others], on the glycemic profile of individuals with type 2 diabetes,” they added.

“When focusing on HbA1c, only ginger and black cumin demonstrated therapeutic effects,” the authors noted. “However, our meta-analysis highlights ginger as an herb with substantial translational potential for diabetes treatment, impacting all three glycemic parameters.”

“Regarding clove, parsley, thyme, black pepper, rosemary, basil, and oregano, more studies are needed to analyze the effect of these herbs on the glycemic profile in type 2 diabetes subjects,” the authors concluded.

SOURCE:

The study was published on March 7, 2024, in Nutrients. The first author was Maria Carmen Garza, PhD, of the Department of Human Anatomy and Histology, School Medicine, University of Zaragoza, Zaragoza, Spain.

LIMITATIONS:

Despite the results, a variety of other factors can affect fasting glucose levels, including changes in body weight or body mass index, as well as the combination of spice or aromatic herb supplementation with physical activity or lifestyle changes, the authors noted.

Due to the studies’ differences, the determination of effective dosages of the herbs and spices was not possible.

Furthermore, the studies had wide variations in quality, with few studies including adequate statistical analysis.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

Bone-modifying agents — most notably denosumab — are often prescribed to prevent skeletal-related complications in patients with metastatic castration-sensitive prostate cancer, but the drugs are not recommended for this indication and can lead to severe toxicities.

How much does Medicare spend each year on non-recommended bone therapy?

The answer, according to a new analysis in JCO Oncology Practice, is more than $44 million, with about $43 million coming from denosumab alone.

Overall, this study found that “the Medicare program pays tens of millions of dollars each year” for bone-modifying agents in patients with metastatic castration-sensitive prostate cancer, “which is not effective and may cause side effects,” lead author Aaron Mitchell, MD, MPH, a medical oncologist at Memorial Sloan Kettering Cancer Center, New York City, and colleagues concluded.

“These findings suggest reducing bone agent overuse could be a rare healthcare ‘win-win.’ Lower costs AND improved patient outcomes,” tweeted Dr. Mitchell. “If I were a payer, I’d be paying attention!”
 

In Prostate Cancer, Bone-Modifying Drug Indications Vary

Bone-modifying drugs are indicated for some patients with prostate cancer.

The American Society of Clinical Oncology has endorsed guidelines that recommend the use of denosumab in men with nonmetastatic prostate cancer at high risk for fracture while taking androgen deprivation therapy.

Among men with metastatic castration-resistant prostate cancer, guidelines also recommend zoledronic acid or denosumab for preventing or delaying skeletal-related events, such as pathologic fractures and spinal cord compression.

For patients with metastatic castration-sensitive disease, however, the bone-modifying agents show no benefit in preventing skeletal-related events and are not recommended for that indication.

In this population, “treatment with bone agents results only in avoidable toxicity and financial cost,” Dr. Mitchell tweeted. In its higher-dose formulation, denosumab comes with a price tag of approximately $40,000 per year in the United States.

An earlier study from Dr. Mitchell and colleagues revealed that the use of bone-modifying drugs to prevent skeletal events in metastatic castration-sensitive prostate cancer is common.

To better understand the costs associated with this inappropriate use, the researchers reviewed Surveillance, Epidemiology, and End Results Program Medicare data from 2011 to 2015. The team identified the frequency and number of doses of zoledronic acid and denosumab prescribed against recommendations in the metastatic castration-sensitive setting, making sure to distinguish between the use of denosumab to prevent osteoporotic fractures (appropriate use) and to prevent skeletal-related events (non-recommended use).

The team found that, among 2627 patients with metastatic castration-sensitive prostate cancer, 42% received at least one dose of denosumab and 18% received at least one dose of zoledronic acid.

The authors also found that unnecessary use of these drugs increased over time — with a little over 17% of patients receiving zoledronic acid between 2007 and 2009 and just over 28% receiving either denosumab (20.3%) or zoledronic acid (8.4%) from 2012 to 2015.

The annual costs to Medicare from non-recommended prescribing came to $44,105,041 for both agents, with the costs associated with denosumab representing the lion’s share at $43,303,078.

Non-recommended use of these agents also came with adverse events, such as femur fracture and hypocalcemia, which cost an estimated $758,450 to treat annually — $682,865 for denosumab and $75,585 for zoledronic acid.

The study focused on the Medicare-age population, which means the estimates are conservative. “Denosumab overuse for younger patients with castration-sensitive prostate cancer would add substantially to this total,” the authors wrote.

“This study contributes new evidence of overuse in the metastatic castrate-sensitive prostate cancer setting, which I must admit reflects my clinical experience in seeing patients for second opinions who are treated in the community,” said Samuel U. Takvorian, MD, of the Division of Hematology and Oncology, Perelman School of Medicine, Philadelphia, who wasn’t involved in the research. “While there are some circumstances in which one would consider using a bone-modifying agent in the metastatic castrate-sensitive prostate cancer setting, most [of these] men don’t need them upfront.”
 

Why Is the Overuse Happening?

One reason for the inappropriate use of bone-modifying drugs could be confusion surrounding the recommendations because the drugs are recommended for some patients with prostate cancer.

Michael R. Laurent, MD, PhD, of Imelda Hospital, Bonheiden, Belgium, explained that the use of bone-modifying drugs is, paradoxically, often overlooked in settings where they are recommended — when patients have an elevated risk for osteoporosis or fracture.

“Guidelines are quite unequivocal in their recommendations to prevent osteoporosis in mostly older men who receive androgen deprivation therapy,” but “I think there is significant undertreatment” in these patients, Dr. Laurent told this news organization.

However, the recommendation for patients at risk for osteoporosis or bone fracture calls for less intense regimens, which may include lower-dose denosumab, administered once every 6 months, zoledronic acid, given yearly, or another lower potency agent, such as oral alendronate weekly, explained Philip J. Saylor, MD, an attending physician at Massachusetts General Hospital and assistant professor at Harvard Medical School, Boston.

Meanwhile, “monthly high-intensity therapy to prevent skeletal events should be reserved specifically for bone metastatic castration-resistant prostate cancer for more than just cost reasons,” Dr. Saylor said.

When it comes to the higher dose, monthly therapy in castration-sensitive prostate cancer, “we have no evidence that it is beneficial,” he said, adding that “when the prostate cancer itself is well controlled by hormonal therapy, there just aren’t very many pathologic fractures or other bone complications.”

Alongside possible confusion over the recommendations, many physicians also likely don’t know how much denosumab costs.

“In our recent physician interview study, we did find that most physicians were very much unaware of the cost of this drug, or the cost difference between denosumab and zoledronic acid, so I do think that lack of cost awareness is a factor,” Dr. Mitchell said.

Part of the reason may be how Medicare covers these agents. Typically, Medicare would not cover non-recommended indications, but “in this case, Medicare coverage is broader and includes both the guideline-recommended and non-recommended uses,” Dr. Mitchell explained.

However, the authors also identified a more cynical reason for non-recommended prescribing — promotional payments from drug makers to physicians.

In another recent paper, Dr. Mitchell said he found about “30% of doctors treating prostate cancer had received payments from Amgen for Xgeva [denosumab] promotion during the last year.”

These payments appeared to influence non-recommended prescribing: Among patients whose doctor had not received payments, 31.4% received non-recommended denosumab, which increased to nearly 50% of patients among doctors who had received payments.

Dr. Mitchell suggested a few ways to help curb inappropriate prescribing.

Medicare could, for instance, change its coverage policy to include only the recommended uses of these agents, Dr. Mitchell said.

More physician education would be another solution. “I think that physician education would be one ‘bottom-up’ approach that could work,” Dr. Mitchell added.

Dr. Mitchell, Dr. Takvorian, and Dr. Saylor had no disclosures to report. Dr. Laurent has received lecture and consultancy fees from Alexion, AM Pharma, Amgen, Galapagos, Kyowa Kirin, Menarini, Orifarm, Pharmanovia, Takeda, UCB, and Will Pharma.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

TOPLINE:

More than a billion children, adolescents, and adults are living with obesity, globally, with rates of obesity among children and adolescents quadrupling between 1990 and 2022.

Obesity rates nearly tripled among adult men and more than doubled among women during the time period, according to results from a collaboration between the NCD Risk Factor Collaboration and the World Health Organization (WHO).

The rates of being underweight have meanwhile declined, making obesity now the most common form of malnutrition in most regions.

METHODOLOGY:

In this global analysis, the authors evaluated 3663 population-based studies conducted in 200 countries and territories, with data on 222 million participants in the general population, including height and weight.

Trends were established according to categories of body mass index (BMI) in groups of adults aged 20 years or older, representing 150 million individuals, and 63 million school-aged children and adolescents aged 5-19 years, spanning from 1990 to 2022.

Assessments of adults focus on the individual and combined prevalence of underweight (BMI < 18.5 kg/m²) and obesity (BMI ≥ 30 kg/m²).

For school-aged children and adolescents, assessments were for thinness (BMI < 2 standard deviation [SD] below the median of the WHO growth reference) and obesity (BMI > 2 SD above the median).

TAKEAWAY:

The combined prevalence of obesity as well as underweight increased over the study period in most countries for women (162 countries, 81%) and men (140 countries, 70%), with increases driven by increases in obesity in nearly all countries, while underweight or thinness rates decreased.

In 2022, obesity rates were higher than underweight in 177 countries (89%) for women and 145 countries (73%) for men.

Likewise, among school-aged children and adolescents, obesity in 2022 was more prevalent than thinness among girls in 130 countries (67%) and boys in 125 countries (63%), while thinness was more prevalent in only 18% and 21% of the countries, respectively.

In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, as well as in countries in the Middle East and North Africa.

Among school-aged children, the countries with the highest combined prevalence of underweight and obesity were Polynesia and Micronesia and the Caribbean for both sexes and Chile and Qatar for boys.

The prevalence of obesity surpassed 60% among women in eight countries (4%) and men in six countries (3%), all in Polynesia and Micronesia.

In the United States, the obesity rate increased from 21.2% in 1990 to 43.8% in 2022 for women and from 16.9% to 41.6% in 2022 for men.

As of 2022, the prevalence of obesity in the United States ranked 36th highest in the world for women and 10th highest in the world for men.

IN PRACTICE:

“It is very concerning that the epidemic of obesity that was evident among adults in much of the world in 1990 is now mirrored in school-aged children and adolescents,” senior author Majid Ezzati, PhD, of Imperial College of London, said in a press statement.

“At the same time, hundreds of millions are still affected by undernutrition, particularly in some of the poorest parts of the world,” he said. “To successfully tackle both forms of malnutrition, it is vital we significantly improve the availability and affordability of healthy, nutritious foods.”

Tedros Adhanom Ghebreyesus, PhD, WHO Director-General, added in the press statement that “this new study highlights the importance of preventing and managing obesity from early life to adulthood, through diet, physical activity, and adequate care, as needed.

“Getting back on track to meet the global targets for curbing obesity will take the work of governments and communities, supported by evidence-based policies from WHO and national public health agencies,” he said.

“Importantly, it requires the cooperation of the private sector, which must be accountable for the health impacts of their products.”

SOURCE:

The study was published on February 29, 2024, in The Lancet. The study was conducted by the NCD Risk Factor Collaboration and the WHO.

LIMITATIONS:

Data differences in countries included that some had limited data and three had none, requiring some estimates to be formed using data from other countries. Data availability was also lower among the youngest and oldest patients, increasing uncertainty of data in those age groups. In addition, data from health surveys can be subject to error, and BMI can be an imperfect measure of the extent or distribution of body fat.

DISCLOSURES:

The study was funded by UK Medical Research Council, UK Research and Innovation, and the European Commission.
 

A version of this article appeared on Medscape.com.

Patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse following hematopoietic stem cell transplant (allo-HCT) show significantly superior survival outcomes when treated with chimeric antigen receptor (CAR) T-cell therapy compared with other novel alternative therapies, a real-world analysis of patients in the UK shows.

“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”

Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.

Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.

With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.

Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).

Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.

The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.

“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”

Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.

With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).

The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).

The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.

“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”

In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.

Dr. Rampotas discloses receiving conference fees from Gilead.

Patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse following hematopoietic stem cell transplant (allo-HCT) show significantly superior survival outcomes when treated with chimeric antigen receptor (CAR) T-cell therapy compared with other novel alternative therapies, a real-world analysis of patients in the UK shows.

“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”

Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.

Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.

With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.

Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).

Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.

The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.

“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”

Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.

With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).

The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).

The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.

“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”

In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.

Dr. Rampotas discloses receiving conference fees from Gilead.

Patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse following hematopoietic stem cell transplant (allo-HCT) show significantly superior survival outcomes when treated with chimeric antigen receptor (CAR) T-cell therapy compared with other novel alternative therapies, a real-world analysis of patients in the UK shows.

“This is the first time there is a real-world comparison of CAR-T cell therapy versus other treatments in the era of other novel therapies such as inotuzumab or tyrosine kinase inhibitors (TKIs),” said first author Alexandros Rampotas, MD, of the University College London Hospital NHS Foundation Trust. “The study was looking retrospectively at patients treated in the UK, but the results should be applicable to most countries where similar treatments are available.”

Dr. Rampotas presented the research at the 6th European CAR T-cell Meeting jointly sponsored by the Society for Blood and Marrow Transplantation and the European Hematology Association.

Outcomes when patients with B-ALL relapse after allo-HCT treatment are generally very poor, and while the advent of CAR T-cell therapy has provided significant improvements, additional novel targeted therapies have also joined the field to further improve outcomes.

With no prior studies directly comparing outcomes between the various treatment options in a real-world setting, Dr. Rampotas and colleagues conducted a retrospective analysis of posttransplant relapsed B-ALL cases at six major transplant centers in the United Kingdom between 2010 and 2022.

Of 93 patients with sufficient data for the analysis, 17 had been treated with CAR T-cell therapy: 4 with UCART19, 1 with CD22 CAR T-cell, and 12 with the CD19-directed CAR T-cell products tisagenlecleucel (Kymriah) or obecabtagene autoleucel (obe-cel).

Among the remaining 75 patients who received non-CAR T-cell therapies, 24 received TKIs, 11 received blinatumumab, 12 received inotuzumab, 10 received intensive chemotherapy, 3 received intensive chemotherapy and TKI therapy, 14 received palliative/supportive regimens and 1 had a second allo-HCT following relapse from the first.

The median time from relapse to treatment was 2.8 months in the CAR T-cell therapy group, and 0.32 months for those receiving non-CAR T-cell therapies.

“The 2.8-month time-to-treat is quite expected as CAR T-cells can take a while to manufacture and be infused,” Dr. Rampotas noted. “This also comes with the bias that the patients who did receive them were likely fitter and could wait for that long.”

Patients receiving CAR T-cell therapy were also younger (median age 26 versus 47 in the non-CAR T-cell group) but the CAR T-cell group had higher risk disease and had a median of 2 prior lines of therapy versus 1 in the non-CAR T-cell group.

With a median follow-up of 24.8 months, patients receiving CAR T-cell therapy had significantly better rates of overall survival (OS), with 31 months compared with the non-CAR T-cell therapy OS of just 6.4 months (P = .0147).

The patients treated with CAR T-cell therapy also had improved progression-free survival (PFS) over the non-CAR T-cell patients (16.7 vs 3.7 months; P = .0001).

The superior outcomes in the CAR T-cell group remained consistent after exclusion of patients who received palliative approaches.

“In the realm of numerous innovative therapies for B-ALL, CAR Ts have now, for the first time, exhibited superior outcomes over alternative approaches in posttransplant relapsed B-ALL in the real world,” the authors reported. “The clear superior PFS and OS should encourage the use of more CAR T-cell therapies for this challenging cohort, while further improvements are imperative to enhance outcomes.”

In the meantime, “patients who relapse post transplant with B-ALL should be referred for CAR-T cell therapy as it is a superior treatment to other available options,” Dr. Rampotas said.

Dr. Rampotas discloses receiving conference fees from Gilead.

A simple prediction model developed with US and European cohorts shows accuracy in identifying patients with relapsed/refractory multiple myeloma (RRMM) who are or are not at high risk for relapsing after treatment with anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) therapy.

“To our knowledge, this large multicenter study is the first report to identify patients with RRMM at high risk of early relapse after CAR-T,” the authors report in the study, published February 15 in the Journal of Clinical Oncology.

“We saw that early relapse within 5 months from infusion was significantly associated with very poor outcomes, and disease-, treatment-, and inflammation-specific variables were independent predictors of early relapse,” first author Nico Gagelmann, MD, of the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, explained in presenting the findings at the 6th European CAR T-cell Meeting jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association. CAR-T therapy has revolutionized the treatment of RRMM, with the idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) CAR-T therapies approved for the condition. However, the treatment is far from a cure, with nearly 50% of patients relapsing and having progression of disease within the first year after infusion, prompting a need to better understand the risk factors for who may or may not progress.

With a lack of a universal model to help with those predictions across products and populations, Dr. Gagelmann and colleagues conducted a retrospective observational study utilizing data from 136 patients at seven CAR-T centers in Europe and 133 patients at three centers in the US who had received either commercial or academically produced anti-BCMA CAR-T.

Of the patients, 171 were infused with ide-cel, 38 with cilta-cel, and 60 with an academic CAR-T therapy. The patients had a median age of 63, and extramedullary disease was more common in the US cohort (48%) versus European (35%; P = .04).

Notably, the response rates between the European and US cohorts were similar, despite various differences between the cohorts, including differences in ethnicities and a lower body mass index (BMI) in the European cohort versus US (BMI 25 vs 28, respectively; P < .001). There were also no significant differences in responses between the CAR-T treatments.

The overall response rate was 87% and was comparable between the European and US groups, with complete responses occurring among 48% of patients in Europe and 49% in the US group.

Their measurable residual disease (MRD) negativity rate at any time was 29% and 37%, respectively, and rates of complete response at day 30 were 29% and 26%, respectively. The rate of progression-free survival at 12 months was 40% for the entire cohort, with a rate of 45% in the European group and 34% in the US group (P = .09). Overall survival rates at 12 months were 79% and 65%, respectively (P = .11).

The patients had a median time to relapse of 5 months, and the 5-month incidence of relapse was identical, at 24% in each cohort.

Of those patients, overall survival at 12 months was low, at 30% in the European cohort and 14% in the US group.

“Early relapse within the first 5 months clearly identified patients with poor survival across the cohort,” Dr. Gagelmann said.

Key Risk Factors Identified

Key factors found after multivariate adjustment to be independently predictive of early relapse or progression included extramedullary disease or plasma cell leukemia, being refractory to lenalidomide, having high-risk cytogenetics, and having increased age- and sex-adjusted ferritin at the time of lymphodepletion.

With each of the risk factors valued at 1 point, the MyCARe model ranked scores of 0-1 points as low-risk, 2-3 as intermediate risk, and a score above 4 was considered high-risk.

Based on the model, the risk of early relapse within 5 months among those scored as low risk was 7%, for intermediate risk, 27% (hazard ratio [HR], 3.27 vs low-risk; P < .001), and for high risk, 53% (HR, 7.89 vs low-risk; P < .001), with outcomes overall comparable between the two geographic groups. Importantly, the model maintained utility for patients who did and did not receive salvage therapies; however, “more studies are needed to identify the optimal post–CAR-T approach,” the authors write.

Dr. Gagelmann added that older age was significantly associated with improved progression-free survival in the US cohort, with a 12-month progression-free survival of 27% among patients under 65 versus 43% for those over 65 (P = .03). However, age was not found to be associated with similar outcomes in the European cohort.

The authors note that the MyCARe model outperformed the CAR-HEMATOTOX and more recent disease-specific R2-ISS risk-stratification tools regarding prediction of relapse/progression and progression-free survival.

However, with CAR-HEMATOTOX developed to predict side effects and non-relapse mortality, “our results demonstrate that both scores independently predict different outcomes after anti–BCMA CAR-T in RRMM,” the authors report. Therefore, “they can be used complimentarily to predict complications (CAR-HEMATOTOX) and relapse/progression-free survival (MyCARe model).”

Importantly, the authors add that the tool may help in patient selection for earlier treatment.

“As ide-cel and cilta-cel have shown astonishing efficacy for earlier treatment lines, our model might also be validated for such patients,” the authors note in the study. They conclude that the study provides “the first Euro-American cartography of the efficacy and safety profile of current CAR-T, showing comparable results.”

“We also built the MyCARe model, which can predict early relapse, response, and survival and may facilitate patient selection in this very challenging setting,” the authors report.
 

Hope for Interventions Based on Patients’ Risk

Commenting on the study, Rahul Banerjee, MD, an assistant professor with the Division of Hematology and Oncology, University of Washington, Seattle, underscored that “we need more cross-border research like this in the myeloma field.”

“Clinically, my hope that this will help us tailor post–CAR-T interventions according to each patient’s risk profile,” he said.

Risk factors such as the presence of extramedullary disease, plasma cell leukemia, or high-risk cytogenetics are expected; however, Dr. Banerjee said the inclusion of increased ferritin before CAR-T was “an interesting new risk factor that we’ve also heard about from our colleagues in the lymphoma space.”

Ferritin perturbations can indicate many things, but high ferritin can be a sign of elevated inflammation at baseline,” he explained. “These patients may have a hyperinflammatory phenotype of their myeloma which can predispose T-cells to exhaustion,” Dr. Banerjee said.

“Exhausted T-cells at collection mean exhausted CAR T-cells at infusion, and so the negative prognostic significance of elevated ferritin — which we don’t always check before CAR-T — makes sense.”

While the authors suggest a potential benefit of the MyCAR3 model in identifying patients who could benefit from other novel therapies at relapse, Dr. Banerjee suggests another possibility. “I’d take this a step further and suggest future studies of this MyCARe model to identify patients who might benefit from post–CAR-T maintenance,” he said.

“The ‘one-and-done’ nature of CAR-T in terms of not requiring further myeloma therapy after infusion is a powerful benefit for patients, but there are some patients who may benefit from low-dose pomalidomide or iberdomide/mezigdomide maintenance to help keep the myeloma at bay and to promote T-cell fitness,” Dr. Banerjee explained. “This risk model may identify patients to prioritize for such types of clinical trials in the future.”

Caveats include that factors beyond the baseline features (used for the risk model) can further influence outcomes,” Dr. Banerjee noted.

“Risk stratification is inherently a dynamic process over time,” he said, questioning, for instance, “what about patients who achieve measurable residual disease negativity [MRD] at day +28 after CAR-T cell? Does the achievement of MRD negativity ‘erase’ a high-risk MyCARe score? We’ll need future studies to tell.”

An overriding take-home message for clinicians should be to simply refer eligible patients to a CAR-T capable center as soon as possible for evaluation.

“In the lymphoma world, they have a nice adage for this: ‘If they recur, you should refer,’ ” he said. “I’d suggest the same here. By no means will we move to CAR-T therapy for every patient at first relapse. However, based on their MyCARe score and other risk factors, there may be patients we prioritize for CAR-T first versus CAR-T with maintenance versus clinical trials.”

Dr. Gagelmann reported relationships with BMS, Pfizer, Stemline, MorphoSys, and Kite. Dr. Banerjee disclosed ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

A simple prediction model developed with US and European cohorts shows accuracy in identifying patients with relapsed/refractory multiple myeloma (RRMM) who are or are not at high risk for relapsing after treatment with anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) therapy.

“To our knowledge, this large multicenter study is the first report to identify patients with RRMM at high risk of early relapse after CAR-T,” the authors report in the study, published February 15 in the Journal of Clinical Oncology.

“We saw that early relapse within 5 months from infusion was significantly associated with very poor outcomes, and disease-, treatment-, and inflammation-specific variables were independent predictors of early relapse,” first author Nico Gagelmann, MD, of the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, explained in presenting the findings at the 6th European CAR T-cell Meeting jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association. CAR-T therapy has revolutionized the treatment of RRMM, with the idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) CAR-T therapies approved for the condition. However, the treatment is far from a cure, with nearly 50% of patients relapsing and having progression of disease within the first year after infusion, prompting a need to better understand the risk factors for who may or may not progress.

With a lack of a universal model to help with those predictions across products and populations, Dr. Gagelmann and colleagues conducted a retrospective observational study utilizing data from 136 patients at seven CAR-T centers in Europe and 133 patients at three centers in the US who had received either commercial or academically produced anti-BCMA CAR-T.

Of the patients, 171 were infused with ide-cel, 38 with cilta-cel, and 60 with an academic CAR-T therapy. The patients had a median age of 63, and extramedullary disease was more common in the US cohort (48%) versus European (35%; P = .04).

Notably, the response rates between the European and US cohorts were similar, despite various differences between the cohorts, including differences in ethnicities and a lower body mass index (BMI) in the European cohort versus US (BMI 25 vs 28, respectively; P < .001). There were also no significant differences in responses between the CAR-T treatments.

The overall response rate was 87% and was comparable between the European and US groups, with complete responses occurring among 48% of patients in Europe and 49% in the US group.

Their measurable residual disease (MRD) negativity rate at any time was 29% and 37%, respectively, and rates of complete response at day 30 were 29% and 26%, respectively. The rate of progression-free survival at 12 months was 40% for the entire cohort, with a rate of 45% in the European group and 34% in the US group (P = .09). Overall survival rates at 12 months were 79% and 65%, respectively (P = .11).

The patients had a median time to relapse of 5 months, and the 5-month incidence of relapse was identical, at 24% in each cohort.

Of those patients, overall survival at 12 months was low, at 30% in the European cohort and 14% in the US group.

“Early relapse within the first 5 months clearly identified patients with poor survival across the cohort,” Dr. Gagelmann said.

Key Risk Factors Identified

Key factors found after multivariate adjustment to be independently predictive of early relapse or progression included extramedullary disease or plasma cell leukemia, being refractory to lenalidomide, having high-risk cytogenetics, and having increased age- and sex-adjusted ferritin at the time of lymphodepletion.

With each of the risk factors valued at 1 point, the MyCARe model ranked scores of 0-1 points as low-risk, 2-3 as intermediate risk, and a score above 4 was considered high-risk.

Based on the model, the risk of early relapse within 5 months among those scored as low risk was 7%, for intermediate risk, 27% (hazard ratio [HR], 3.27 vs low-risk; P < .001), and for high risk, 53% (HR, 7.89 vs low-risk; P < .001), with outcomes overall comparable between the two geographic groups. Importantly, the model maintained utility for patients who did and did not receive salvage therapies; however, “more studies are needed to identify the optimal post–CAR-T approach,” the authors write.

Dr. Gagelmann added that older age was significantly associated with improved progression-free survival in the US cohort, with a 12-month progression-free survival of 27% among patients under 65 versus 43% for those over 65 (P = .03). However, age was not found to be associated with similar outcomes in the European cohort.

The authors note that the MyCARe model outperformed the CAR-HEMATOTOX and more recent disease-specific R2-ISS risk-stratification tools regarding prediction of relapse/progression and progression-free survival.

However, with CAR-HEMATOTOX developed to predict side effects and non-relapse mortality, “our results demonstrate that both scores independently predict different outcomes after anti–BCMA CAR-T in RRMM,” the authors report. Therefore, “they can be used complimentarily to predict complications (CAR-HEMATOTOX) and relapse/progression-free survival (MyCARe model).”

Importantly, the authors add that the tool may help in patient selection for earlier treatment.

“As ide-cel and cilta-cel have shown astonishing efficacy for earlier treatment lines, our model might also be validated for such patients,” the authors note in the study. They conclude that the study provides “the first Euro-American cartography of the efficacy and safety profile of current CAR-T, showing comparable results.”

“We also built the MyCARe model, which can predict early relapse, response, and survival and may facilitate patient selection in this very challenging setting,” the authors report.
 

Hope for Interventions Based on Patients’ Risk

Commenting on the study, Rahul Banerjee, MD, an assistant professor with the Division of Hematology and Oncology, University of Washington, Seattle, underscored that “we need more cross-border research like this in the myeloma field.”

“Clinically, my hope that this will help us tailor post–CAR-T interventions according to each patient’s risk profile,” he said.

Risk factors such as the presence of extramedullary disease, plasma cell leukemia, or high-risk cytogenetics are expected; however, Dr. Banerjee said the inclusion of increased ferritin before CAR-T was “an interesting new risk factor that we’ve also heard about from our colleagues in the lymphoma space.”

Ferritin perturbations can indicate many things, but high ferritin can be a sign of elevated inflammation at baseline,” he explained. “These patients may have a hyperinflammatory phenotype of their myeloma which can predispose T-cells to exhaustion,” Dr. Banerjee said.

“Exhausted T-cells at collection mean exhausted CAR T-cells at infusion, and so the negative prognostic significance of elevated ferritin — which we don’t always check before CAR-T — makes sense.”

While the authors suggest a potential benefit of the MyCAR3 model in identifying patients who could benefit from other novel therapies at relapse, Dr. Banerjee suggests another possibility. “I’d take this a step further and suggest future studies of this MyCARe model to identify patients who might benefit from post–CAR-T maintenance,” he said.

“The ‘one-and-done’ nature of CAR-T in terms of not requiring further myeloma therapy after infusion is a powerful benefit for patients, but there are some patients who may benefit from low-dose pomalidomide or iberdomide/mezigdomide maintenance to help keep the myeloma at bay and to promote T-cell fitness,” Dr. Banerjee explained. “This risk model may identify patients to prioritize for such types of clinical trials in the future.”

Caveats include that factors beyond the baseline features (used for the risk model) can further influence outcomes,” Dr. Banerjee noted.

“Risk stratification is inherently a dynamic process over time,” he said, questioning, for instance, “what about patients who achieve measurable residual disease negativity [MRD] at day +28 after CAR-T cell? Does the achievement of MRD negativity ‘erase’ a high-risk MyCARe score? We’ll need future studies to tell.”

An overriding take-home message for clinicians should be to simply refer eligible patients to a CAR-T capable center as soon as possible for evaluation.

“In the lymphoma world, they have a nice adage for this: ‘If they recur, you should refer,’ ” he said. “I’d suggest the same here. By no means will we move to CAR-T therapy for every patient at first relapse. However, based on their MyCARe score and other risk factors, there may be patients we prioritize for CAR-T first versus CAR-T with maintenance versus clinical trials.”

Dr. Gagelmann reported relationships with BMS, Pfizer, Stemline, MorphoSys, and Kite. Dr. Banerjee disclosed ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

A simple prediction model developed with US and European cohorts shows accuracy in identifying patients with relapsed/refractory multiple myeloma (RRMM) who are or are not at high risk for relapsing after treatment with anti–B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) therapy.

“To our knowledge, this large multicenter study is the first report to identify patients with RRMM at high risk of early relapse after CAR-T,” the authors report in the study, published February 15 in the Journal of Clinical Oncology.

“We saw that early relapse within 5 months from infusion was significantly associated with very poor outcomes, and disease-, treatment-, and inflammation-specific variables were independent predictors of early relapse,” first author Nico Gagelmann, MD, of the University Medical Center Hamburg-Eppendorf, in Hamburg, Germany, explained in presenting the findings at the 6th European CAR T-cell Meeting jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association. CAR-T therapy has revolutionized the treatment of RRMM, with the idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) CAR-T therapies approved for the condition. However, the treatment is far from a cure, with nearly 50% of patients relapsing and having progression of disease within the first year after infusion, prompting a need to better understand the risk factors for who may or may not progress.

With a lack of a universal model to help with those predictions across products and populations, Dr. Gagelmann and colleagues conducted a retrospective observational study utilizing data from 136 patients at seven CAR-T centers in Europe and 133 patients at three centers in the US who had received either commercial or academically produced anti-BCMA CAR-T.

Of the patients, 171 were infused with ide-cel, 38 with cilta-cel, and 60 with an academic CAR-T therapy. The patients had a median age of 63, and extramedullary disease was more common in the US cohort (48%) versus European (35%; P = .04).

Notably, the response rates between the European and US cohorts were similar, despite various differences between the cohorts, including differences in ethnicities and a lower body mass index (BMI) in the European cohort versus US (BMI 25 vs 28, respectively; P < .001). There were also no significant differences in responses between the CAR-T treatments.

The overall response rate was 87% and was comparable between the European and US groups, with complete responses occurring among 48% of patients in Europe and 49% in the US group.

Their measurable residual disease (MRD) negativity rate at any time was 29% and 37%, respectively, and rates of complete response at day 30 were 29% and 26%, respectively. The rate of progression-free survival at 12 months was 40% for the entire cohort, with a rate of 45% in the European group and 34% in the US group (P = .09). Overall survival rates at 12 months were 79% and 65%, respectively (P = .11).

The patients had a median time to relapse of 5 months, and the 5-month incidence of relapse was identical, at 24% in each cohort.

Of those patients, overall survival at 12 months was low, at 30% in the European cohort and 14% in the US group.

“Early relapse within the first 5 months clearly identified patients with poor survival across the cohort,” Dr. Gagelmann said.

Key Risk Factors Identified

Key factors found after multivariate adjustment to be independently predictive of early relapse or progression included extramedullary disease or plasma cell leukemia, being refractory to lenalidomide, having high-risk cytogenetics, and having increased age- and sex-adjusted ferritin at the time of lymphodepletion.

With each of the risk factors valued at 1 point, the MyCARe model ranked scores of 0-1 points as low-risk, 2-3 as intermediate risk, and a score above 4 was considered high-risk.

Based on the model, the risk of early relapse within 5 months among those scored as low risk was 7%, for intermediate risk, 27% (hazard ratio [HR], 3.27 vs low-risk; P < .001), and for high risk, 53% (HR, 7.89 vs low-risk; P < .001), with outcomes overall comparable between the two geographic groups. Importantly, the model maintained utility for patients who did and did not receive salvage therapies; however, “more studies are needed to identify the optimal post–CAR-T approach,” the authors write.

Dr. Gagelmann added that older age was significantly associated with improved progression-free survival in the US cohort, with a 12-month progression-free survival of 27% among patients under 65 versus 43% for those over 65 (P = .03). However, age was not found to be associated with similar outcomes in the European cohort.

The authors note that the MyCARe model outperformed the CAR-HEMATOTOX and more recent disease-specific R2-ISS risk-stratification tools regarding prediction of relapse/progression and progression-free survival.

However, with CAR-HEMATOTOX developed to predict side effects and non-relapse mortality, “our results demonstrate that both scores independently predict different outcomes after anti–BCMA CAR-T in RRMM,” the authors report. Therefore, “they can be used complimentarily to predict complications (CAR-HEMATOTOX) and relapse/progression-free survival (MyCARe model).”

Importantly, the authors add that the tool may help in patient selection for earlier treatment.

“As ide-cel and cilta-cel have shown astonishing efficacy for earlier treatment lines, our model might also be validated for such patients,” the authors note in the study. They conclude that the study provides “the first Euro-American cartography of the efficacy and safety profile of current CAR-T, showing comparable results.”

“We also built the MyCARe model, which can predict early relapse, response, and survival and may facilitate patient selection in this very challenging setting,” the authors report.
 

Hope for Interventions Based on Patients’ Risk

Commenting on the study, Rahul Banerjee, MD, an assistant professor with the Division of Hematology and Oncology, University of Washington, Seattle, underscored that “we need more cross-border research like this in the myeloma field.”

“Clinically, my hope that this will help us tailor post–CAR-T interventions according to each patient’s risk profile,” he said.

Risk factors such as the presence of extramedullary disease, plasma cell leukemia, or high-risk cytogenetics are expected; however, Dr. Banerjee said the inclusion of increased ferritin before CAR-T was “an interesting new risk factor that we’ve also heard about from our colleagues in the lymphoma space.”

Ferritin perturbations can indicate many things, but high ferritin can be a sign of elevated inflammation at baseline,” he explained. “These patients may have a hyperinflammatory phenotype of their myeloma which can predispose T-cells to exhaustion,” Dr. Banerjee said.

“Exhausted T-cells at collection mean exhausted CAR T-cells at infusion, and so the negative prognostic significance of elevated ferritin — which we don’t always check before CAR-T — makes sense.”

While the authors suggest a potential benefit of the MyCAR3 model in identifying patients who could benefit from other novel therapies at relapse, Dr. Banerjee suggests another possibility. “I’d take this a step further and suggest future studies of this MyCARe model to identify patients who might benefit from post–CAR-T maintenance,” he said.

“The ‘one-and-done’ nature of CAR-T in terms of not requiring further myeloma therapy after infusion is a powerful benefit for patients, but there are some patients who may benefit from low-dose pomalidomide or iberdomide/mezigdomide maintenance to help keep the myeloma at bay and to promote T-cell fitness,” Dr. Banerjee explained. “This risk model may identify patients to prioritize for such types of clinical trials in the future.”

Caveats include that factors beyond the baseline features (used for the risk model) can further influence outcomes,” Dr. Banerjee noted.

“Risk stratification is inherently a dynamic process over time,” he said, questioning, for instance, “what about patients who achieve measurable residual disease negativity [MRD] at day +28 after CAR-T cell? Does the achievement of MRD negativity ‘erase’ a high-risk MyCARe score? We’ll need future studies to tell.”

An overriding take-home message for clinicians should be to simply refer eligible patients to a CAR-T capable center as soon as possible for evaluation.

“In the lymphoma world, they have a nice adage for this: ‘If they recur, you should refer,’ ” he said. “I’d suggest the same here. By no means will we move to CAR-T therapy for every patient at first relapse. However, based on their MyCARe score and other risk factors, there may be patients we prioritize for CAR-T first versus CAR-T with maintenance versus clinical trials.”

Dr. Gagelmann reported relationships with BMS, Pfizer, Stemline, MorphoSys, and Kite. Dr. Banerjee disclosed ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.

Reports of a small number of patients developing secondary T-cell malignancies following treatment with chimeric antigen receptor (CAR) T-cell immunotherapy have raised concerns and prompted a class-wide boxed warning to the labeling of the therapies by the US Food and Drug Administration (FDA), but for now experts underscore that the benefits of the groundbreaking therapies still appear to well outweigh the risks.

Importantly, most specialists agree, so far the risk appears no greater than the known risk of secondary primary malignancies that is well established with other cancer therapies.

“The data that we have so far suggest that the risk of secondary T-cell lymphoma in patients treated with CAR T-cells is similar to [that] of patients treated with other cancer therapies, [including] chemotherapy, radiation, transplantation,” Marco Ruella, MD, said in an interview. He reported on a case of a T-cell lymphoma occurring following CAR-T therapy at the University of Pennsylvania.

While his team is still investigating the development of such malignancies, “the FDA notice does not change our clinical practice and patients should be reassured that the benefit of CAR-T therapy significantly outweighs the potential risk of secondary malignancies including T-cell lymphoma,” said Dr. Ruella, scientific director of the Lymphoma Program, Division of Hematology and Oncology and Center for Cellular Immunotherapies, at the University of Pennsylvania, Philadelphia.
 

FDA: 28 Reports of Malignancies; 3 with Evidence of ‘Likely’ CAR T Involvement

Concerns were raised last November when the FDA announced in a safety communication that it was investigating the “serious risk of T-cell malignancy” following B-cell maturation antigen (BCMA)-directed or CD19-directed CAR T-cell immunotherapies, citing reports from clinical trials and/or postmarketing adverse event data sources. Subsequently, in January, the FDA called for the boxed warning on all approved BCMA- and CD19-targeted genetically modified autologous T-cell immunotherapies, which include: Abecma (idecabtagene vicleucel); Breyanzi (lisocabtagene maraleucel); Carvykti (ciltacabtagene autoleucel); Kymriah (tisagenlecleucel); Tecartus (brexucabtagene autoleucel); and Yescarta (axicabtagene ciloleucel).

“Although the overall benefits of these products continue to outweigh their potential risks for their approved uses, the FDA continues to investigate the identified risk of T-cell malignancy with serious outcomes, including hospitalization and death,” the FDA reported in discussing the safety warnings.

The cases were detailed in a report from FDA researchers published in the New England Journal of Medicine, noting that as of December 31, 2023, the FDA had become aware of 22 cases of T-cell cancers occurring following CAR T-cell treatment, including T-cell lymphoma, T-cell large granular lymphocytosis, peripheral T-cell lymphoma, and cutaneous T-cell lymphoma.

Report coauthor Peter Marks, MD, PhD, of the FDA’s Center for Biologics Evaluation and Research in Silver Spring, Maryland, said in an interview that since the publication of their report, six new cases have emerged.

“As reported in the NEJM Perspective, there were 22 cases of T-cell malignancy after treatment with CAR T-cell immunotherapies as of December 31, 2023, but we have received additional reports and, as of February 9, 2024, FDA has now received 28 reports,” he said. “Note that as new cases are being reported, there will be updates to the total number of cases under ongoing review by FDA.”

The initial 22 cases all occurred relatively soon after treatment. Of 14 cases with sufficient data, all developed within 2 years of the CAR-T therapy, ranging from 1 to 19 months, with about half occurring in the first year after administration.

The cases involved five of the six FDA-approved CAR-T products, with the numbers too low to suggest an association with any particular product.

In three of the cases, the lymphoma was found in genetic testing to contain the CAR construction, “indicating that the CAR-T product was most likely involved in the development of the T-cell cancer,” according to the FDA researchers.

With inadequate genetic sampling in most of the remaining 19 cases, the association is less clear, however “the timing of several of the cases makes association a possibility,” Dr. Marks said. In their report, Dr. Marks and colleagues added that “determination of whether the T-cell cancer is associated with the CAR construct ... most likely won’t be possible for every case reported to date.”

Even if all the reported cases are assumed to be related to CAR-T treatment, the numbers still represent a very small proportion of the more than 27,000 doses of the six CAR-T therapies approved in the United States, the authors noted, but they cautioned that the numbers could indeed be higher than reported.

“Relying on postmarketing reporting may lead to underestimates of such cases,” they said.
 

Life-Long Monitoring Recommended

In response to the reports, the FDA is urging that clinicians’ monitoring of patients treated with CAR-T therapy should be lifelong.

“Patients and clinical trial participants receiving treatment with these products should be monitored lifelong for new malignancies,” Dr. Marks said.

“In the event that a new malignancy occurs following treatment with these products, contact the manufacturer to report the event and obtain instructions on collection of patient samples for testing for the presence of the CAR transgene.”

In addition, cases should be reported to the FDA, either by calling or through the FDA’s medical product safety reporting program.
 

T-Cell Malignancy Case Report

In describing the case at their medical center in the report in Nature Medicine, Dr. Ruella and colleagues said a T-cell lymphoma occurred in a patient with non-Hodgkin B-cell lymphoma 3 months after an anti-CD19 CAR T-cell treatment.

As a result, the team conducted a subsequent analysis of 449 patients treated with CAR-T therapy at the University of Pennsylvania center, and with a median follow-up of 10.3 months, 16 patients (3.6%) had developed a secondary primary malignancy, with a median onset time of 26.4 months for solid and 9.7 months for hematological malignancies.

The patient who had developed a T-cell lymphoma tested negative for CAR integration upon diagnosis, and regarding the other cancers, Dr. Ruella noted that “we have no indication that the secondary malignancies are directly caused by the CAR-T therapy.

“We have many patients with a very long follow-up beyond 5 and even 10 years,” he said. “In these patients, we don’t see an increased risk of T-cell lymphoma.”
 

‘Cautious Reassurance’ Urged in Discussion with Patients

With alarming headlines on the findings suggesting that CAR-T therapy may cause cancer, Rahul Banerjee, MD, and colleagues at the University of Washington, Seattle, recommend the use of “cautious reassurance” in discussing the issue with patients. In a paper published in January in Blood Advances, they suggest a three-part response: underscoring that the benefits of CAR T “far outweigh” the risks in relapsed/refractory malignancies, that the ‘one-and-done’ nature of CAR-T infusions provide meaningful improvements in quality of life, and that the active cancer at hand is “a much larger threat than a hypothetical cancer years later.”

In many cases, patients may only have months to live without CAR-T therapy and will have already had multiple prior lines of therapy, therefore the CAR-T treatment itself may provide time for the secondary primary cancers from any of the treatments to emerge, as experts have noted.

“One has to be alive to be diagnosed with a secondary primary malignancy, and it’s thus very possible that CAR-T may be creating a type of ‘immortal time bias’ wherein patients live long enough to experience the unfortunate sequelae of their previous therapies,” Dr. Banerjee explained in an interview.

Nevertheless, the potential for substantial improvements in quality of life with CAR-T therapy compared with traditional treatments addresses a top priority for patients, he added.

“For most patients with [for instance], myeloma, the ability of CAR-T to put them rapidly into a deep remission without the need for maintenance is an unheard-of potential for them,” Dr. Banerjee said.

“In multiple myeloma, no CAR-T therapy has (yet) demonstrated an overall survival benefit — but I think the substantial quality-of-life benefit stands by itself as a big reason why patients continue to prefer CAR-T.”
 

Keep Patients In Touch with CAR T Centers

In light of the concerns regarding the secondary malignancies, Dr. Banerjee underscored that CAR-T patients should be kept in close touch with centers that have CAR-T treatment expertise.

With most patients followed primarily at community practices where CAR-T therapy is not administered, “I’d strongly encourage my colleagues in community practices to refer all eligible patients to a CAR-T-capable center for evaluation regardless of what their risk of post-CAR-T secondary primary malignancies may be,” Dr. Banerjee urged.

“Based on the evidence we have currently, which includes the FDA’s updated information, there are many more unknowns about this potential secondary primary malignancy risk than knowns,” he said. “This is of course a much more nuanced issue than any one package insert can convey, and CAR-T experts at treating centers can have these conversations at length with eligible patients who are nervous about these recent updates.”

Dr. Ruella disclosed that he holds patents related to CD19 CAR T cells, as well as relationships with NanoString, Bristol Myers Squibb, GlaxoSmithKline, Scailyte, Bayer, AbClon, Oxford NanoImaging, CURIOX, and Beckman Coulter, and he was the scientific founder of viTToria Biotherapeutics. Dr. Banerjee reported ties with BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures, Novartis, and Pack Health.