COPENHAGEN—The PD-1 checkpoint inhibitor nivolumab can address an unmet need in patients with classical Hodgkin lymphoma (cHL) who have progressive or relapsed disease, according to a speaker at the 21st Congress of the European Hematology Association.
In the phase 2 Checkmate-205 trial, nivolumab produced an objective response rate of 66% in cHL patients who had relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and subsequent brentuximab vedotin.
The median duration of response was 7.8 months, and most patients had a response that was ongoing at the time of analysis.
Although the safety profile of nivolumab was considered “acceptable” by researchers, the drug has been linked to serious complications, including death, among patients who proceeded to allogeneic HSCT after receiving nivolumab.
Still, nivolumab is “an important new therapy to meet the unmet need” in cHL, according to Anas Younes, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Dr Younes presented results with nivolumab from cohort B of the Checkmate-205 trial as abstract S793. Checkmate-205 was sponsored by Bristol-Myers Squibb.
Cohort B included 80 cHL patients who had relapsed or progressed after autologous HSCT and post-transplant brentuximab vedotin. (Cohort A included patients who had not previously received brentuximab vedotin.)
The patients’ median age was 37 (range, 18-72), and 64% were male. The median number of prior lines of therapy was 4 (range, 3-15), and 49% of patients had received at least 5 previous lines of therapy.
Seventy-four percent of patients had previously received radiation, 93% had received 1 prior autologous HSCT, and 8% had received 2. All patients had received brentuximab vedotin after transplant, and 54% had not responded to that treatment.
Study treatment
Patients received nivolumab at 3 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.
At a median follow-up of 8.9 months (range, 1.9-11.7), 36% of patients had come off treatment—16% due to disease progression, 5% due to toxicity, 8% because they had gone on to allogeneic HSCT, and 8% for other reasons (the patient’s request, the investigator’s decision, the patient was lost to follow-up, or the reason was not reported).
Dr Younes noted that all patients who stopped nivolumab to undergo HSCT were still alive at the data cut-off.
Efficacy
The objective response rate, per an independent radiologic review committee, was 66%. Nine percent of patients achieved a complete response, 58% had a partial response, 23% had stable disease, and 8% had progressive disease. The committee was unable to determine the status of 4% of patients.
The median time to response was 2.1 months, and the estimated median duration of response was 7.8 months.
“Keep in mind that the majority of patients are still on therapy, so this is expected to improve with time,” Dr Younes said.
The majority of responses (62%) were ongoing at the time of analysis. In an exploratory analysis, the researchers observed that 72% of patients who did not respond to their most recent prior brentuximab vedotin treatment did respond to nivolumab.
At 6 months, the progression-free survival rate was 77%, and the overall survival rate was 99%. The median progression-free survival was 10 months, and the median overall survival has not been reached.
Dr Younes said that, although the follow-up is short, the survival data are “still impressive.”
Safety
Adverse events (AEs) occurred in 99% of patients, grade 3/4 AEs occurred in 40% of patients, and there was 1 grade 5 AE (multi-organ failure due to Epstein-Barr-virus-positive T-cell lymphoma).
Treatment-related AEs occurred in 90% of patients. The most common of these were fatigue (25%), infusion-related reactions (20%), rash (16%), arthralgia (14%), pyrexia (14%), nausea (13%), diarrhea (10%), and pruritus (10%).
Treatment-related serious AEs occurred in 6% of patients and included pyrexia, tumor progression, arrhythmia, infusion reactions, septic meningitis, and pneumonia.
Extended safety follow-up of cHL patients treated in the nivolumab clinical trial program who were subsequently treated with allogeneic HSCT (n=17) revealed complications, including fatal events.
A warning about such complications has been added to the US prescribing information for nivolumab, which was recently granted accelerated approval from the US Food and Drug Administration (FDA) to treat patients with relapsed or refractory cHL who have received an autologous HSCT and post-transplant brentuximab vedotin.
Because of these transplant-related deaths, the FDA has advised that healthcare professionals follow patients closely for early evidence of transplant-related complications, such as hyperacute graft-versus-host disease, severe acute graft-versus-host disease, steroid-requiring febrile syndrome, hepatic veno-occlusive disease, and other immune-mediated adverse reactions.
The FDA has also required that Bristol-Myers Squibb further study the safety of allogeneic HSCT after nivolumab.
