Micrograph showing HL
LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).
In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.
Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.
“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.
Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.
CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:
- Cohort A included patients who were naïve to BV (n=63)
- Cohort B included patients who received BV only after auto-HSCT (n=80)
- Cohort C included patients who received BV before and/or after auto-HSCT (n=100).
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 were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.
Patient characteristics
The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.
ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.
The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.
The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.
The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.
The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.
Safety
The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).
The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).
Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).
There were no deaths due to drug-related AEs.
Response
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.
Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.
SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.
In post-hoc analyses, responses were similar irrespective of BV treatment sequence.
The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.
The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.
The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.
Survival
The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.
The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.
The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.
Patient status after extended follow-up
Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.
The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.
Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.
Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.
None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.
Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.
Outcomes after allo-HSCT
Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).
At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%. At 6 months, the rates were 30%, 20%, and 15%, respectively.
The incidence of transplant-related mortality was 13% at 100 days and at 6 months.
“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.
She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.
