According to results from an extended follow-up of the CheckMate-205 trial looking at patients with relapsed/refractory classical Hodgkin lymphoma after autologous hematopoietic cell transplantation, nivolumab (Opdivo) caused an overall objective response rate of 69%.
Philippe Armand, MD
According to results from an extended follow-up of the CheckMate-205 trial looking at patients with relapsed/refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic cell transplantation (auto-HCT), nivolumab (Opdivo) induced an overall objective response rate (ORR) of 69%.1
An independent review committee (IRC) found an ORR of 69% (95% CI, 63%-75%) while 16% of the patients had complete response (CR) and 53% had partial response (PR). The ORR was 72%, with 33% of patients achieving CR.
“Sustained benefits were seen across different patient populations, including patients refractory to prior therapies and patients with and without prior BV (brentuximab vedotin [Adcetris]) exposure, and were not dependent on achieving CR,” first author Philippe Armand, MD, Dana-Farber Cancer Institute, and colleagues wrote.
“The exploratory analyses presented here lend further support to the hypothesis that PD-1 blockade may provide durable benefit even in patients who do not achieve objective responses, including a subset of patients who experience conventional progressive disease. Altogether, the results of this study suggest that nivolumab treatment may provide long-term benefits to a broad spectrum of patients with relapsed/refractory cHL after auto-HCT," Armand added.
From August 2014 to August 2015, CheckMate-205, a single-arm trial, enrolled patients at 34 sites in North America and Europe. Patients were divided into a BV-naïve cohort (A; n = 63), a BV following failure with auto-HCT cohort (B; n = 80), and a BV following failure before and/or after auto-HCT cohort (C; n = 100).
All patients in the trial received 3 mg/kg of nivolumab every 2 weeks until disease progression or unacceptable toxicity. Patients in cohort C discontinued nivolumab after 1 year in persistent CR and had the option to resume treatment if they relapsed within 2 years of the last dose.
With a median follow-up of 18 months, ORR was assessed by IRC of 65% in cohort A, 68% in cohort B, and 73% in cohort C. Over 95% of patients had reductions in target lesion burden.
Response rates were about the same in patients who received brentuximab vedotin after auto-HCT (71%; 95% CI, 63-78) or only before auto-HCT (70%; 95% CI, 51-84). ORR was also found to be similar in patients who were refractory to their first or last line of therapy, at 73% and 68%, respectively, or to BV given after auto-HCT, at 68%.
Overall median time to first objective response was 2.1 months (IQR, 1.9-2.7). Overall median IRC-assessed duration of response (DOR) was 16.6 months (95% CI, 13.2-20.3). The median DOR was 20.3 months in in cohort A, 15.9 months in cohort B, and 14.5 months in cohort C.
Median DOR was 16.6 months (95% CI, 12.8not estimable) in patients refractory to their first (n = 103) or last (n = 77) line of therapy and 16.6 months (95% CI, 9.5–not estimable) in patients refractory to their most recent line of BV after auto-HCT (n = 51).
Median overall progression-free survival (PFS) was 14.7 months (95% CI, 11.3-18.5). Median PFS was 18.3 months in cohort A, 14.7 months in cohort B, and 11.9 months in cohort C. Median PFS was comparable for patients who received BV after (11.9 months) or only before (11.5 months) auto-HCT.
The median time to next treatment was not reached in cohorts A and B, and while cohort C had found 19.4 months (95% CI, 14.8not estimable).
Median overall survival (OS) was not reached in any of the cohorts or in patients grouped by any best overall response. The 1-year OS rate was 92% (95% CI, 88-95) overall, 93% (95% CI, 83-98) in cohort A, 95% (95% CI, 87-98) in cohort B, and 90% (95% CI, 82-94) in cohort C.
The most common grade 3/4 drug-related adverse events (AEs) were lipase increases (5%), neutropenia (3%), and ALT increases (3%).
Additionally, 29 patients died in the study, while 18 of those deaths were due to disease progression. All deaths were considered unrelated to the study drug.
Inevstigators also noted 17 patients (7%) discontinued treatment because of drug-related AEs. Serious drug-related AEs occurred in 12% of patients, most commonly infusion-related reactions (2%).
In an accompanying podcast, Andrew M. Evens, DO, director of the lymphoma program and associate director for clinical services at the Rutgers Cancer Institute of New Jersey said the results demonstrated high and durable responses in the majority of patients and that clinical benefit with treatment past conventional progression was a potential “paradigm-changing concept of drug therapy.”2
“Continued research is needed to more fully harmonize the differences seen in response rates, particularly CR rates, between investigators and the IRC,” Evens said. “Longer follow-up and additional experience is warranted to confirm all of the highly encouraging findings reported here, and continued translational studies are needed to identify potential predictive biomarkers of efficacy and safety of checkpoint inhibitor therapy in lymphoma.”
The FDA granted nivolumab an accelerated approval in May 2016 for treatment of patients with cHL that have relapsed or progressed after autologous hematopoietic stem cell transplantation and posttransplantation BV. This approval was based on results from a combined analysis of patients with relapsed or refractory cHL who received nivolumab either in the CheckMate-205 trial or CheckMate-039 trial.