ABCL-454: CheckMate 436: Extended Follow-Up from the Phase 2 Study Investigating Nivolumab Plus Brentuximab Vedotin (BV) for Relapsed/Refractory Primary Mediastinal Large B-Cell Lymphoma (R/R PMBL)

Abstract

Context R/R PMBL has limited treatment options. CheckMate 436 (NCT02581631), an open-label phase 1/2 study, assessed combination nivolumab (anti–PD-1) and brentuximab vedotin (anti-CD30) in patients with R/R PMBL; the primary analysis (median follow-up 11.1 months) showed an objective response rate (ORR) of 73% and complete remission (CR) rate of 37%. Objective Report extended follow-up data from CheckMate 436. Patients Cohort of patients with R/R PMBL after autologous hematopoietic cell transplantation (auto-HCT) or ≥2 prior multi-agent chemotherapy regimens if ineligible for auto-HCT. Interventions Nivolumab (240 mg IV) + BV (1.8 mg/kg IV) every 3 weeks until disease progression or unacceptable toxicity. Outcome Measure(s) Primary: investigator-assessed ORR (Lugano 2014) and safety. Secondary: duration of response (DOR), CR rate and duration, progression-free survival (PFS), and overall survival (OS). Results Among 30 patients with a median follow-up of 33.7 months, ORR was 73% (95% CI, 54–88; CR, 37%). Median DOR was 31.6 months (95% CI, 23.3–not estimable [NE]), and median duration of CR was not reached. Estimated median PFS was 26.0 months (95% CI, 2.6–NE). Among patients censored in the PFS analysis, 13/17 received consolidation therapy, including auto-HCT (n=6) or allogeneic HCT (n=6) +/- radiotherapy, and radiotherapy alone (n=1). Four patients remained progression free in follow-up for 5+, 9+, 12+, and 20+ months after discontinuation of nivolumab + BV (maximum clinical benefit, n=3; study drug toxicity, n=1) without subsequent therapy. OS was 79% (95% CI, 59–90) at 12 months and 76% (95% CI, 55–88) at 24 months; median OS was not reached. Treatment-related adverse events (TRAEs) occurred in 83% of patients, most frequently neutropenia (30%; all grade 3/4) and peripheral neuropathy (27%; 10% grade 3/4). Six patients discontinued due to TRAEs. Eight patients died, 5 due to disease progression, and none was considered related to treatment. Conclusions Nivolumab + BV demonstrated durable responses and long-term survival benefits; 4 patients remained progression-free without consolidation after nivolumab + BV. Safety was consistent with prior findings. These results further support nivolumab + BV as a treatment option for patients with R/R PMBL. Funding BMS. Previous Presentation: ICML 2021