NIVOLUMAB PLUS DOXORUBICIN, VINBLASTINE AND DACARBAZINE FOR NEWLY DIAGNOSED ADVANCED‐STAGE CLASSICAL HODGKIN LYMPHOMA: CHECKMATE 205 COHORT D 2‐YEAR FOLLOW‐UP

Abstract

Introduction: Up to 30% of patients (pts) with advanced-stage (AS) classical Hodgkin lymphoma (cHL) are not cured by current front-line therapies (Tx). High expression of programmed death-1 (PD-1) ligands in these pts, associated with frequent genetic alterations at chromosome 9p24.1 in Hodgkin Reed–Sternberg cells, supports the investigation of front-line PD-1 blockade in cHL. Promising activity and acceptable safety were reported in newly diagnosed pts with AS cHL treated with nivolumab, an anti–PD-1 immune checkpoint inhibitor monoclonal antibody, followed by nivolumab plus doxorubicin, vinblastine and dacarbazine (N-AVD) at a 9-mo follow-up of CheckMate 205 Cohort D (NCT02181738). Here, we report the efficacy and safety of this cohort in a 2-y extended follow-up, including Deauville assessment of tumor response. Results: Fifty-one pts were treated (median age 37 y); minimum follow-up was 24.4 mo at data cut-off. Other baseline characteristics have been previously described (Ramchandren R et al. EHA 2018). Monotherapy was completed by 49/51 (96%) pts, combination Tx by 45/50 (90%); 48 pts entered follow-up. After 2 combination cycles, CR rate was 51% per IRC (71% CMR) and 71% per investigator; at EOT, CR rate was 69% (75% CMR) per IRC and 80% per investigator. At 21 mo, mPFS rate per investigator was 80% (95% CI, 66–89) and PFS rate per investigator was 83% (95% CI, 69–91; Figure). Overall, 30 (59%) pts experienced grade (G) 3–4 TRAEs, most commonly neutropenia in 21 (41%). The most common G 3–4 immune-mediated AE was hepatitis (2 pts, 4%). No G 5 TRAEs occurred ≤ 30 d from last dose; 2 deaths were reported during the extended follow-up: 1 pt (aged 68 y) died 38 d after last dose due to study drug toxicity; another (aged 85 y) died 451 d after last dose due to disease progression. Conclusions: With extended follow-up, nivolumab followed by N-AVD demonstrated a 21-mo PFS rate of 83% per investigator, a high metabolic response rate with 75% CMR at EOT per IRC, with no new safety signals. Incorporation of Deauville assessment improved the concordance of CR between IRC- and investigator-assessed responses. Nivolumab followed by N-AVD provides a promising alternative Tx option in newly diagnosed AS cHL. Keywords: classical Hodgkin lymphoma (cHL); nivolumab; PD-1. Disclosures: Ansell, S: Honoraria: WebMD, Research to Practice; Research Funding: Affimed Therapeutics (Inst), Bristol-Myers Squibb (Inst), Merck (Inst), Regeneron (Inst), Seattle Genetics (Inst), Trillium Therapeutics (Inst), Pfizer (Inst). Ramchandren, R: Consultant Advisory Role: Bristol-Myers Squibb, Seattle Genetics; Research Funding: Merck, Pharmacyclics, Janssen. Domingo-Domènech, E: Honoraria: Bristol-Myers Squibb, Takeda; Other Remuneration: Travel, Accommodations, Expenses: Bristol-Myers Squibb, Roche, Takeda. Rueda, A: Consultant Advisory Role: Bristol-Myers Squibb, Merck, MSD, Novartis, Roche, Takeda; Honoraria: Bristol-Myers Squibb, Merck, MSD, Roche. Trněný, M: Consultant Advisory Role: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Gilead Sciences, Incyte, Janssen, MorphoSys, Roche, Takeda; Honoraria: AbbVie, Amgen, Bristol-Myers Squibb, Gilead Sciences, Incyte, Janssen, MorphoSys, Roche, Takeda; Other Remuneration: Travel, Accommodations, Expenses: AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche, Takeda. Feldman, T: Consultant Advisory Role: Bristol-Myers Squibb, Seattle Genetics; Honoraria: Takeda; Research Funding: Portola (Inst), Seattle Genetics (Inst); Other Remuneration: Celgene, Pharmacyclics, Seattle Genetics, KITE, Johnson and Johnson, Janssen. Lee, H: Employment Leadership Position: MD Anderson Cancer Center; Consultant Advisory Role: Bristol-Myers Squibb; Honoraria: Bristol-Myers Squibb; Research Funding: Bristol-Myers Squibb, Celgene, Oncternal. Provencio, M: Consultant Advisory Role: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Takeda, Roche, Novartis, Pfizer; Honoraria: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Boerhinger; Research Funding: Roche, Boerhinger, Bristol-Myers Squibb. Cohen, J: Consultant Advisory Role: AbbVie, Celgene, Genentech, Pharmacyclics, Seattle Genetics; Research Funding: American Society of Hematology, Bristol-Myers Squibb, Lam Therapeutics, Lymphoma Research Foundation, Novartis, Seattle Genetics, Takeda, Unum Therapeutics. Savage, K: Consultant Advisory Role: AbbVie, Bristol-Myers Squibb, Merck, Seattle Genetics, Servier, Verastem; Honoraria: Bristol-Myers Squibb, Merck, Seattle Genetics, Takeda; Research Funding: Roche (Inst). Willenbacher, W: Consultant Advisory Role: Bristol-Myers Squibb, Takeda; Honoraria: Bristol-Myers Squibb, Takeda; Research Funding: Bristol-Myers Squibb, Takeda. Sumbul, A: Employment Leadership Position: Bristol-Myers Squibb. Sacchi, M: Employment Leadership Position: Bristol-Myers Squibb. Armand, P: Consultant Advisory Role: Affimed Therapeutics, Bristol-Myers Squibb, Infinity Pharmaceuticals, Merck, Pfizer, Adaptive; Research Funding: Affimed Therapeutics (Inst), Bristol-Myers Squibb (Inst), Merck (Inst), Otsuka (Inst), Pfizer (Inst), Roche (Inst), Sequenta (Inst), Sigma Tau (Inst), Tensha Therapeutics (Inst), Adaptive (inst); Other Remuneration: Travel, Accommodations, Expenses: Genmab.