Nivolumab can provide “long-term benefits” in patients with relapsed or refractory classical Hodgkin lymphoma (cHL), according to researchers.
Extended follow-up of the CheckMate-205 study showed that nearly 70% of patients responded to nivolumab.
The median duration of response was 17 months, and the median progression-free survival (PFS) was 15 months.
The most common drug-related AEs were fatigue, diarrhea, infusion-related reactions, rash, nausea, and pruritus.
Philippe Armand, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, and his colleagues reported these results in the Journal of Clinical Oncology.
The study was sponsored by Bristol-Myers Squibb Company.
This phase 2 trial enrolled 243 adults with relapsed or refractory cHL who had undergone autologous hematopoietic stem cell transplant (auto-HSCT).
Their median age was 34 (range, 26-46), and 58% were male. Fifty-seven percent had stage IV disease, 20% had stage III, 21% had stage II, and 2% had stage I.
Patients had received a median of 4 prior therapies (range, 3-5). The median time from diagnosis to first nivolumab dose was 4.5 years (range, 2.4-7.6), and the median time from most recent auto-HSCT to first nivolumab dose was 2.0 years (range, 0.9-4.9).
The researchers divided patients into 3 cohorts according to exposure to brentuximab vedotin (BV):
- Cohort A was BV-naïve (n=63)
- Cohort B received BV only after auto-HSCT (n=80)
- Cohort C received BV before and/or after auto-HSCT (n=100).
Baseline characteristics were generally similar across the cohorts. However, cohort A had fewer prior treatments (median of 2 vs 4 in cohorts B and C).
Cohort B had the longest interval between diagnosis and first nivolumab dose (6.2 years vs 3.1 in cohort A and 3.5 in C) and between most recent auto-HSCT and first nivolumab dose (3.4 years vs 1 in cohort A and 1.7 in C).
All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.
In cohort C, patients who were in complete response (CR) for 1 year had to discontinue nivolumab, but they could resume treatment if they relapsed within 2 years.
A protocol amendment allowed patients to continue treatment despite progression if they had stable performance status and were deriving “perceived clinical benefit.”
At a median follow-up of 18 months, 40% percent of all patients were still on treatment, including 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.
The most common drug-related AEs were fatigue (23%), diarrhea (15%), infusion-related reactions (14%), rash (12%), nausea (10%), and pruritus (10%).
The most common grade 3/4 drug-related AEs were lipase increase (5%), neutropenia (3%), ALT increase (2%), AST increase (2%), and amylase increase (2%).
The most common serious drug-related AEs were infusion-related reactions (2%), pneumonitis (1%), pneumonia (1%), pleural effusion (1%), and pyrexia (1%).
Seven percent of patients discontinued treatment due to AEs. The most common of these were pneumonitis (2%) and autoimmune hepatitis (1%).
There were no deaths due to drug-related AEs.
The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.
CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.
The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, 15 months for cohort C, and 20 months for patients who achieved a CR.
The researchers said responses were similar irrespective of BV treatment sequence.
The median PFS was 15 months for all patients, 18 months for cohort A, 15 months for cohort B, 12 months for cohort C, and 22 months for patients who achieved a CR.
The median overall survival was not reached in any of the cohorts.
The 12-month overall survival was 92% overall, 93% in cohort A, 95% in cohort B, 90% in cohort C, and 100% in patients who achieved a CR.
Forty-four patients proceeded to allogeneic HSCT after nivolumab, and the median post-HSCT follow-up was 5.5 months (range, 2.9-11.8).
At 6 months, the rate of transplant-related mortality was 13%, and the rate of disease progression was 7%.
The rate of grade 2-4 acute graft-vs-host disease (GVHD) was 30%, the rate of grade 3-4 acute GVHD was 20%, and the rate of chronic GVHD was 15%.