Feature

Survival on the upswing in myeloma


 

When hematologist James R. Berenson, MD, began practicing medicine in the 1980s, his 45-year-old cousin Stanley broke his ribs while hugging his son in a swimming pool. The cousin was a well-respected orthopedic surgeon in Los Angeles, but his specialty could do nothing for him. Stanley had the bone-ravaging disease known as multiple myeloma (MM).

Back then, the treatments for MM were chemotherapy and steroids. Stem-cell transplants were on the horizon, as was a most unexpected therapy: the infamous drug thalidomide.

But in the wake of the rib facture, the health of Stanley Katz, MD, worsened and he died after 25 weeks, Dr. Berenson recalled in an interview. At that time, Dr. Katz’s horrifically shortened lifespan following diagnosis was not unusual.

About 4 decades later, hematologists like Dr. Berenson are heralding a new era in MM, a sharp reversal of the previous eras of grim prognoses.

In a new study, Dr. Berenson tracked 161 patients with MM treated at his West Hollywood, Calif., private clinic from 2006 to 2023 and found that their median survival was 136.2 months – more than 11 years. “The OS reported in this study ... is the longest reported to date in an unselected, newly diagnosed MM population,” the study authors write.

Dr. Berenson’s patients are unique: They’re largely White, and they didn’t undergo stem-cell transplants. But other recent studies also suggest that lifespans of more than 10 years are increasingly possible after MM diagnosis. Former TV news anchor Tom Brokaw, for one, has reached that point.

In fact, a pair of other hematologists say the overall survival in Dr. Berenson’s report is hardly out of the question. And, they say, patients diagnosed today could potentially live even longer, because treatments continue to improve.

“With data that’s 10 years old, we expect the median overall survival to be 10 years,” hematologist Sagar Lonial, MD, who’s been tracking survival data in MM, said in an interview. “When patients ask about my outlook, I say it’s a constantly evolving field. Things are changing fast enough that I use 10 years as a floor.”

Dr. Lonial is chair of the department of hematology and medical oncology and chief medical officer at Emory University, Atlanta, Winship Cancer Institute.

Hematologist Rafael Fonseca, MD, chief innovation officer at Mayo Clinic–Arizona, put it this way in an interview: Dr. Berenson’s results “are probably in sync with what we would anticipate with similar cohorts of patients. The reality is that we’ve seen a huge improvement in the life expectancy of patients who were diagnosed with multiple myeloma. It’s not unusual to see patients in the clinic now that are 15 or 20 years out from their diagnosis.”

According to Yale Medicine, MM accounts for 10% of blood cancers and 1%-2% of all cancers and is more common in men vs. women and Blacks vs. Whites. It’s most frequently diagnosed between the ages of 65 and 74, according to the National Cancer Institute, and the median age at diagnosis is 69.

Among the most famous American people currently battling MM are newsman Mr. Brokaw, the former NBC News anchor, and Republican Congressman Steve Scalise, majority leader of the U.S. House of Representatives and a candidate for House speaker.

Mr. Brokaw was diagnosed in 2013 while in his early 70s and has talked about his intense struggle with the disease: the infections, operations, infusions, and daily regimens of 24 pills.

“I didn’t want to be Tom Brokaw, cancer victim,” he said in 2018 at the annual meeting of the American Society of Hematology. But he opened up about his illness, and became “the multiple myeloma poster boy.”

Rep. Scalise, who’s in his late 50s, is undergoing chemotherapy. He survived being gravely wounded in an assassination attempt in 2017.

Dr. Berenson’s new study, published in Targeted Oncology, tracked 161 patients (89 women, 72 men; median age, 65.4; 125 White, 3 Black, 10 Hispanic, 15 Asian, and 8 multi-ethnic).

All started frontline treatment at Dr. Berenson’s clinic and were included if they could read consent forms and gave permission for blood draws. None underwent stem-cell transplants as part of initial therapy. Another 1,036 patients had been treated elsewhere and were not included in the study.

Over a median of 42.7 months (range, 1.9-195.1), the 1-, 3-, and 5-year survival rates were 97.5%, 85.3%, and 76.2%, respectively.

The study claims “these results are considerably better than those reported from patients enrolled in clinical trials and those from countries with national registries.”

In the interview, Dr. Berenson said the study is unique because it’s not limited like many studies to younger, healthier patients. Nor does it include those treated at other facilities, he said.

The study is unusual in other ways. Dr. Berenson said his drug regimens aren’t necessarily standard, and he doesn’t treat patients with stem-cell transplants. “I stopped transplanting in about 2000 because clearly it was not improving the length of life,” he said.

Dr. Berenson said colleagues can learn from his insistence on sensitively treating the quality of life of patients, his embrace of clinical trials with novel combinations, and his close monitoring of myeloma proteins to gauge whether patients need to rapidly switch therapies.

He noted that his drug regimens are typically off-label and vary by patient. “We’re not using as high doses of drugs like Velcade [bortezomib] or Revlimid [lenalidomide] as my colleagues. We’re not necessarily giving as many doses. Also, we’re not adding as many drugs in many cases as they are. We’re taking it slower.”

The National Comprehensive Cancer Network recommends bortezomib and lenalidomide as standard induction treatments in patients with MM who are candidates for stem-cell transplantation, a procedure it considers the “preferred approach in transplant-eligible patients.”

There are limitations to Dr. Berenson’s new study. The patients aren’t representative of people with MM as a whole: His cohort is overwhelmingly White (78%) and just 2% Black, while an estimated one-fifth of patients with MM in the United States are Black and have poorer outcomes.

Dr. Berenson also acknowledged that his patients are most likely a wealthier group, although he said it’s not feasible to ask them about income. The study provides no information about socioeconomics.

Dr. Lonial said survival of 10-11 years is fairly typical in MM, with standard-risk patients reaching 14 years.

He highlighted a 2021 Canadian study that tracked 3,030 patients with newly diagnosed MM from 2007 to 2018 (average age, 64; 58.6% men). Those who received an upfront autologous stem-cell transplant had a median overall survival of 122.0 months (95% confidence interval, 115.0-135.0 months) vs. 54.3 months (95% CI, 50.8-58.8 months) for those who didn’t get the transplants. Not surprisingly, survival dipped with each subsequent treatment regimen.

Dr. Lonial is coauthor of a 2020 study that tracked 1,000 consecutive patients (mean age, 61; 35.2% Black) with newly diagnosed myeloma who were treated with RVD (lenalidomide, bortezomib, and dexamethasone) induction therapy from 2007 to 2016. The median overall survival was 126.6 months (95% CI, 113.3-139.8 months).

Dr. Fonseca noted that the news about MM survival rates is not entirely positive. Patients with high-risk disease often die early on in their disease course, he said.

Research suggests even the youngest patients with MM may die within years of diagnosis. A 2021 French study tracked 214 patients in the 18-40 age group for 15 years (2000-2015). At 5 years, “relative survival compared with same age- and sex-matched individuals was 83.5%,” and estimated overall survival was 14.5 years.

Still, a “very, very fertile environment for the development of drugs” has made a huge difference, Dr. Fonseca said. “We’ve had about 19 FDA approvals in the last 15 or 20 years.”

He urged colleagues to keep in mind that survival drops as patients decline in a line of therapy and need to switch to another one. “It might make intuitive sense to say ‘I’m gonna save something for later. I want to keep my powder dry.’ But put your best foot forward. Always go with your best treatments first.”

This approach can play out in a decision, say, to start with a four-drug initial regimen instead of a weaker two-drug regimen, he said. “Be mindful of managing toxicities, but hit harder.”

As he noted, side effects were worse with older generations of drugs. In regard to cost, multidrug treatments can cost hundreds of thousands of dollars. Dr. Fonseca said insurance tends to cover drugs that are approved by guidelines.

Dr. Fonseca discloses relationships with AbbVie, Adaptive Biotechnologies, Amgen, AstraZeneca, Bayer, Binding Site, BMS (Celgene), Millennium Takeda, Janssen, Juno, Kite, Merck, Pfizer, Pharmacyclics, Regeneron, Sanofi, Adaptive Biotechnologies, Caris Life Sciences, Oncotracker, Antegene, and AZBio, and a patent in MM. Dr. Berenson discloses ties with Janssen, Amgen, Sanofi, BMS, Karyopharm, and Incyte. Dr. Lonial reports ties with TG Therapeutics, Celgene, BMS, Janssen, Novartis, GlaxoSmithKline, AbbVie, Takeda, Merck, Sanofi, Pfizer, Regeneron, and Novartis.

Next Article: