A Phase II Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma

Abstract The programmed death-1 (PD-1) axis can suppress immune surveillance against multiple myeloma (MM). We tested the safety and efficacy of pembrolizumab, an anti-PD-1 antibody, in MM after autologous hematopoietic cell transplantation (AHCT). We enrolled MM patients not achieving complete response (CR) to induction to receive 9 doses of 3- weekly IV pembrolizumab starting day 14 post-AHCT. The primary endpoint was CR rate at end-of-treatment (EOT) in patients receiving >2 pembrolizumab doses. Thirty-two patients were enrolled but 3 withdrew consent prior to receiving the first dose. The study was terminated early after failing to meet its interim analysis endpoint to detect a 20% difference in EOT CR rate conversion. The median age was 59 years. All except 1 received triplet induction for a median 4 cycles (range, 2-7), with 69% partial response (PR) and 31% very good PR (VGPR). No grade 4/5 toxicities or graft failures occurred. Among 26 evaluable patients, 23 had an EOT evaluation and 31% (7/23) achieved CR. Two had EOT serologic CR but no BM confirmation (CRu), while 1 had no EOT evaluation. Bone marrow was minimal residual disease-negative by flow cytometry in 75% (12/16) at day+180. With a median follow-up of 23.7 months (15.1-33.5), no patient achieving EOT CR/CRu had relapsed, while 3 progressed before EOT and one 8 months after EOT VGPR. Estimated 2-year progression-free rate was 83% (95% CI, 68-100). Early post-AHCT pembrolizumab with lenalidomide maintenance was feasible; however, the efficacy is uncertain and needs to be better studied. This trial was registered at www.clinicaltrials.gov as #NCT02331368.