NIVOLUMAB PLUS BRENTUXIMAB VEDOTIN FOR RELAPSED/REFRACTORY PRIMARY MEDIASTINAL LARGE B‐CELL LYMPHOMA: EXTENDED FOLLOW‐UP FROM THE PHASE 2 CHECKMATE 436 STUDY

Introduction: Patients (pts) with relapsed/refractory (R/R) primary mediastinal B-cell lymphoma (PMBL) have poor outcomes and limited treatment options. PMBL is characterized by increased programmed death-1 (PD-1) ligand expression and weak CD30 expression. The combination of nivolumab (NIVO), an anti–PD-1 immune checkpoint inhibitor, and brentuximab vedotin (BV), an anti-CD30 antibody–drug conjugate, has been assessed in pts with R/R PMBL in the open-label, phase 1/2 CheckMate 436 study (NCT02581631); in the primary analysis (median follow-up [FU] 11.1 months) NIVO + BV showed an ORR of 73% and complete remission (CR) rate of 37% (Zinzani et al. J Clin Oncol 2019). We report efficacy and safety data after extended FU. Methods: The expansion cohort of CheckMate 436 enrolled pts with R/R PMBL after autologous hematopoietic cell transplantation (auto-HCT) or ≥2 prior multi-agent chemotherapy regimens if ineligible for auto-HCT. Pts received NIVO (240 mg IV) + BV (1.8 mg/kg IV) every 3 weeks until disease progression or unacceptable toxicity. Primary endpoints were investigator-assessed ORR per Lugano 2014 criteria and safety. Secondary endpoints were duration of response (DOR), CR rate, duration of CR, progression-free survival (PFS), and overall survival (OS). Results: Among 30 pts, median age was 35.5 years. At a median FU of 33.7 months, ORR was 73% (95% CI, 54–88) and CR rate was 37%. Median DOR was 31.6 months (95% CI, 23.3–not estimable [NE]) and median duration of CR was not reached (95% CI, 27.9–NE) The Kaplan–Meier estimate of median PFS was 26.0 months (95% CI, 2.6–NE; Figure). Among the 17 censored pts in the PFS analysis, 13 received consolidation therapy, including auto-HCT (n = 6) or allogeneic-HCT (n = 6) with or without radiotherapy (RT), and RT alone (n = 1); of pts with assessments 1 year after auto-HCT and allo-HCT, 5/6 and 5/5 had CR, respectively. Four pts remained progression-free in FU for 137+, 273+, 372+, and 606+ days after discontinuation of NIVO + BV (3 due to maximum clinical benefit and 1 due to study drug toxicity) without receiving subsequent therapy. The OS rate was 79% (95% CI, 59–90) at 12 months and 76% (95% CI, 55–88) at 24 months; median OS was not reached. Any-grade treatment-related adverse events (TRAEs) occurred in 83% of pts, most frequently neutropenia (30%; all grade 3–4) and peripheral neuropathy (27%; 10% grade 3–4). TRAEs led to discontinuation in 6 pts. No graft-versus-host disease was reported in the 6 pts receiving subsequent allo-HCT. There were 8 deaths, 5 due to disease progression and none considered related to study drug toxicity. The research was funded by: Bristol Myers Squibb Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies, Immunotherapy Conflicts of interests pertinent to the abstract P. L. Zinzani Consultant or advisory role: Servier, Merck, Janssen, Eusapharma, Takeda, Incyte, Gilead, Novartis Honoraria: Servier, Merck, Janssen, Eusapharma, Takeda, Incyte, Gilead, Novartis A. Santoro Consultant or advisory role: Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanofi Other remuneration: Takeda, Bristol Myers Squibb, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, Merck Sharp & Dohme G. Gritti Consultant or advisory role: Takeda, IQvia, Gilead Sciences Honoraria: Amgen, Roche Research funding: Gilead Sciences Educational grants: Roche, Abbvie, Gilead Sciences, Abbvie P. Brice Honoraria: MDS, Takeda P. M. Barr Consultant or advisory role: Bristol Myers Squibb, AbbVie, Janssen, Genentech, TG therapeutics, Gilead, Merck, Morphosys, Bayer, Seattle Genetics, Beigene, MEI J. Kuruvilla Consultant or advisory role: AbbVie, Bristol Myers Squibb, Gilead, Karyopharm, Merck, Roche, Seattle Genetics Honoraria: Amgen, Antengene, Astra Zeneca, Bristol Myers Squibb, Gilead, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle Genetics, TG Therapeutics Research funding: Canadian Cancer Society, Leukemia and Lymphoma Society Canada, Princess Margaret Cancer Foundation, Janssen, Roche, AstraZeneca Other remuneration: Karyopharm (DSMB) D. Cunningham Consultant or advisory role: OVIBIO on Scientific Advisory Board Research funding: Amgen, Sanofi, Merrimack, AstraZeneca, Celgene, MedImmune, Bayer, 4SC, Clovis, Eli Lilly, Janssen, Merck J. Kline Consultant or advisory role: Merck Honoraria: Kite/Gilead, MorphoSys, Karyopharm, Verastem, Seagen Research funding: Merck, iTeos, Verastem N. A. Johnson Consultant or advisory role: Merck, Bristol Myers Squibb, Roche, Seattle Genetics, AbbVie, Jansson, Gilead Honoraria: Roche Research funding: AbbVie, Roche N. Mehta-Shah Consultant or advisory role: Kiowa Hakka Kirin, Karyopharm Therapeutics, C4 Therapeutics, Daiichi Sankyo, Ono Pharmaceuticals, Secura Bio Research funding: Bristol Myers Squibb, Celgene, Verastem, Innate Pharmaceuticals, Corvus Pharmaceuticals, Genentech/Roche M. Fanale Employment or leadership position: Seattle Genetics Stock ownership: Seattle Genetics S. Francis Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb A. J. Moskowitz Honoraria: Imbrium Therapeutics L.P., Merck, and Seattle Genetics Research funding: Miragen, Seattle Genetics, Merck, Bristol Myers Squibb, and Incyte SESSION 8: PERIPHERAL T/NK-CELL LYMPHOMAS

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