NIVOLUMAB FOR RELAPSED OR REFRACTORY (R/R) CLASSICAL HODGKIN LYMPHOMA (CHL) AFTER AUTOLOGOUS TRANSPLANTATION: 5‐YEAR OVERALL SURVIVAL FROM THE PHASE 2 CHECKMATE 205 STUDY (2021)

Introduction: PD-1 immune checkpoint inhibitors, including the monoclonal antibody nivolumab (NIVO), have shown strong activity in patients (pts) with R/R cHL. The pivotal phase 2 CheckMate 205 study (NCT02181738) demonstrated an objective response rate (ORR) of 69%, a median duration of response (DOR) of 17 mo, and median progression-free survival (PFS) of 15 mo in pts with R/R cHL treated with NIVO after autologous hematopoietic cell transplantation (auto-HCT), with a median follow-up of 18 mo (Armand et al. J Clin Oncol 2018). Recently, PD-1 inhibitor monotherapy showed significantly improved PFS vs brentuximab vedotin (BV) in R/R cHL (Kuruvilla et al. ASCO 2020). However, long-term survival benefit of anti–PD-1 therapy and optimal duration of treatment (tx) are unknown. We present updated results of CheckMate 205 with a median follow-up of 58 mo. Methods: CheckMate 205 enrolled pts with R/R cHL after auto-HCT failure into cohorts by tx history: BV-naive (cohort A), BV after auto-HCT (cohort B), and BV before and/or after auto-HCT (cohort C). Pts received NIVO 3 mg/kg every 2 wk until disease progression or unacceptable toxicity. Pts in cohort C discontinued nivo after 1 y in complete remission (CR) and could resume if they relapsed within 2 y. The primary endpoint was ORR per independent radiologic review committee (IRRC); other endpoints included CR, DOR, PFS, overall survival (OS), and safety. Results: Overall, 243 pts were treated (63, 80, and 100 in cohorts A, B, and C, respectively). Baseline characteristics were previously described. Median duration of tx was 14 mo. ORR was 71% (95% CI, 65–77) with a CR rate of 21%. Median PFS was 15 mo (95% CI, 11–19) and median DOR was 18 mo (95% CI, 15–26). Pts with CR had longer median PFS (37 mo) and DOR (30 mo) than pts with partial remission (PR; 15 and 13 mo, respectively). The 2-y and 5-y OS rates (95% CI) were 87% (82–91) and 71% (65–77), and PFS rates were 37% (30–44) and 18% (12–25), respectively. Pts with CR also had improved OS; failure to achieve disease control was a poor prognostic factor for OS (Figure). Per protocol, 12 pts in cohort C stopped study tx after ≥ 1 y of CR. At time of analysis, after a median of 48 mo (range 36–55) from last tx, 6 pts were still in response; 3 were re-treated with NIVO after disease progression (2 re-achieved CR and 1 PR). No new toxicities were observed, and the most common tx-related adverse events (TRAEs) of any grade were fatigue (25%), diarrhea (17%), and rash (12%), almost all grade 1–2. Grade 3–4 TRAEs occurred in 68 pts (28%). TRAEs led to discontinuation in 26 pts (11%). There were no tx-related deaths. The research was funded by: Bristol Myers Squibb Keywords: Hodgkin lymphoma, Immunotherapy Conflicts of interests pertinent to the abstract S. M. Ansell Research funding: Bristol Myers Squibb, Takeda, Seagen, AI Therapeutics, Regeneron, Trillium, Affimed, ADC Therapeutics P. J. Bröckelmann Consultant or advisory role Takeda Honoraria: Bristol Myers Squibb, Takeda Research funding: BeiGene, Bristol Myers Squibb, Merck Sharp & Dohme, Takeda Educational grants: Celgene H. J. Lee Consultant or advisory role Bristol Myers Squibb, Kite Pharma Honoraria: Aptitude Health, Pharmacyclics, Cancer Experts, Guidepoint Global Research funding: Bristol Myers Squibb/Celgene, Takeda, Seattle Genetics, Janssen, Merck, Oncternal, Onyx A. Santoro Consultant or advisory role Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, Merck Sharp & Dohme, Arqule, Sanofi Other remuneration: Speaker's bureau: Takeda, Bristol Myers Squibb, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer, Merck Sharp & Dohme P. L. Zinzani Consultant or advisory role Servier, Merck, Janssen, Eusapharma, Takeda, Incyte, Gilead, Novartis Honoraria: Servier, Merck, Janssen, Eusapharma, Takeda, Incyte, Gilead, Novartis G. P. Collins Consultant or advisory role Bristol Myers Squibb, Merck Sharp & Dohme, Gilead, Roche, Takeda, Incyte, Daiichi Sankyo, BeiGene, Novartis, ADC Therapeutics Honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Gilead, Roche, Takeda, Incyte, Daiichi Sankyo, BeiGene, Novartis, ADC Therapeutics Research funding: Bristol Myers Squibb, Merck Sharp & Dohme, Celleron, BeiGene, Amgen, Pfizer J. B. Cohen Consultant or advisory role BeiGene, Pharmacyclics, Adaptive, Aptitude Health, Gilead/Kite, Adicet, AstraZeneca Research funding: Bristol Myers Squibb/Celgene, Novartis, Genentech, Takeda, LAM, Loxo/Lilly, AstraZeneca, BeiGene J. Kuruvilla Consultant or advisory role Abbvie, Bristol Myers Squibb, Gilead, Karyopharm, Merck, Roche, Seattle Genetics Honoraria: Amgen, Antengene, AstraZeneca, 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) K. J. Savage Consultant or advisory role Bristol Myers Squibb, Merck, Seattle Genetics, Gilead, AstraZeneca, Novartis, Janssen, Kyowa, Servier Other remuneration: Steering committee: BeiGene M. Trneny Consultant or advisory role Roche, Takeda, Bristol Myers Squibb, Incyte, Abbvie, Amgen, Gilead Sciences, Janssen, MorphoSys, Novartis Honoraria: Roche, Janssen, Gilead Sciences, Takeda, Bristol Myers Squibb, Amgen, Abbvie, MorphoSys, Novartis Educational grants: Gilead Sciences, Bristol Myers Squibb, Roche, Janssen, Abbvie, Takeda M. Provencio Consultant or advisory role Bristol Myers Squibb, Merck Sharp & Dohme, AstraZeneca, Takeda, Roche, Lilly Research funding: Bristol Myers Squibb, Roche U. Jaeger Consultant or advisory role Bristol Myers Squibb, Celgene Honoraria: Bristol Myers Squibb, Celgene R. Swanink Employment or leadership position: Bristol Myers Squibb M. Sacchi Employment or leadership position: Bristol Myers Squibb M. A. Shipp Consultant or advisory role Immunitas Therapeutics, AstraZeneca Research funding: Bristol Myers Squibb, Merck, Bayer, AbbVie A. Engert Consultant or advisory role Takeda, ADC Therapeutics, Tessa Pharmaceuticals Honoraria: Bristol Myers Squibb, Takeda, Novartis, Merck Sharp & Dohme, ONO Pharma, Hexal, AstraZeneca Research funding: Bristol Myers Squibb, Takeda, Affimed P. Armand Consultant or advisory role Merck, Bristol Myers Squibb, Pfizer, Affimed, Adaptive, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, AstraZeneca, Genentech Honoraria: Merck, Bristol Myers Squibb Research funding: Merck, Bristol Myers Squibb, Affimed, Adaptive, Genentech, IGM, Kite