Nivolumab Delivers Durable Response in Hodgkin Lymphoma at 18 Months

Philippe Armand, MD, PhD

In an extended follow-up of results from the CheckMate-205 trial, nivolumab (Opdivo) induced an overall objective response rate (ORR) of 69% in patients with relapsed/refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic cell transplantation (auto-HCT).¹

ORR was 69% (95% CI, 63%-75%)as assessed by an independent review committee (IRC). Sixteen percent of patients had complete response (CR) and 53% had partial response (PR). Per investigator assessment, 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.”

CheckMate-205 is a single-arm trial conducted at 34 sites in North America and Europe from August 2014 to August 2015. Patients in the study 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 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 could resume treatment if they relapsed within 2 years of the last dose.

After a median follow-up of 18 months, ORR as assessed by IRC was 65% in cohort A, 68% in cohort B, and 73% in cohort C. More than 95% of patients had reductions in target lesion burden.

Response rates were similar 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 similar among 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, 12.8—not 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 similar for patients who received BV after (11.9 months) or only before (11.5 months) auto-HCT.

Median time to next treatment was not reached in cohorts A and B, and was 19.4 months (95% CI, 14.8—not estimable) in cohort C.

Median overall survival (OS) was not reached overall, in any cohort, 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.

Lipase increases (5%), neutropenia (3%), and ALT increases (3%) were the most common grade 3/4 drug-related adverse events (AEs).

Twenty-nine patients died in the study, most (n = 18) due to disease progression. All deaths were considered unrelated to the study drug.

Seventeen 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,” he 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.”

In May 2016, the FDA granted nivolumab an accelerated approval for the treatment of patients with cHL that has relapsed or progressed after autologous hematopoietic stem cell transplantation and posttransplantation BV. The approval was based on a combined analysis of patients with relapsed or refractory cHL who received nivolumab either in the CheckMate-205 trial or CheckMate-039 trial.

References

1. Armand P, Engert A, Younes A, et al. Nivolumab for relapsed/refractory classic Hodgkin lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm phase II CheckMate 205 Trial [published online March 27, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.76.0793.
2. Evens AM. An international phase II trial of single-agent nivolumab for Hodgkin lymphoma relapsed or refractory after autologous stem cell transplant [podcast]. J Clin Oncol. doi: 10.1200/JCO.2017.76.0793.