A Phase 2 Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma
Anita D'Souza, Parameswaran Hari, Marcelo Pasquini, Thomas Braun, Bryon Johnson, Steven Lundy, Daniel Couriel, Mehdi Hamadani, John Magenau, Binod Dhakal, Nirav N Shah, Mary Riwes, Brian Parkin, Pavan Reddy, Attaphol Pawarode, Anita D'Souza, Parameswaran Hari, Marcelo Pasquini, Thomas Braun, Bryon Johnson, Steven Lundy, Daniel Couriel, Mehdi Hamadani, John Magenau, Binod Dhakal, Nirav N Shah, Mary Riwes, Brian Parkin, Pavan Reddy, Attaphol Pawarode
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 patients with MM who did not achieve a complete response (CR) to induction therapy. The study intervention involved a total of 9 doses of i.v. pembrolizumab, with 1 dose given every 21 days starting on day +14 post-AHCT. The primary endpoint was the rate of CR at end of treatment (EOT) in patients receiving ≥2 pembrolizumab doses. Thirty-two patients were enrolled, but 3 withdrew consent before 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 patient age was 59 years. All but 1 patient received triplet induction for a median of 4 cycles (range, 2 to 7 cycles), 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 7 of these 23 (31%) achieved CR. Two patients had EOT serologic CR but no bone marrow confirmation (CRu), and 1 patient had no EOT evaluation. Bone marrow was minimal residual disease-negative by flow cytometry in 12 of 16 patients (75%) at day +180. With a median follow-up of 23.7 months (range, 15.1 to 33.5 months), no patient achieving EOT CR/CRu had relapsed, whereas 3 patients progressed before EOT and 1 patient progressed at 8 months after EOT VGPR. The estimated 2-year progression-free rate was 83% (95% confidence interval, 68% to 100%). Our data show that early post-AHCT pembrolizumab with lenalidomide maintenance is feasible; however, the efficacy is uncertain and requires further study. This trial was registered at ClinicalTrials.gov (NCT02331368).
Keywords: Autologous transplantation; Checkpoint inhibitor; Lymphodepletion; Multiple myeloma; Pembrolizumab; Post-transplantation.
Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
Source: PubMed