Allogeneic Stem Cell Transplantation in Participants With Hematologic Malignancies Following Pembrolizumab Therapy.

Abstract

Background: The safety and efficacy of allogeneic stem cell transplantation (allo-SCT) following anti-programmed cell death protein 1 (PD-1) therapy in participants with hematologic malignances is of high clinical interest.

Objective: To present outcomes in participants enrolled in 4 clinical trials who underwent allo-SCT within 2 years of their last dose of pembrolizumab therapy.

Study design: This analysis included participants from the phase 1b KEYNOTE-013 study (n = 20), the phase 2 KEYNOTE-087 study (n = 31), the phase 2 KEYNOTE-170 study (n = 5), and the phase 3 KEYNOTE-204 study (n = 14). Outcomes of interest included acute and chronic graft-versus-host disease (GVHD), progression-free survival (PFS) and overall survival (OS), transplant-related mortality (TRM), and relapse.

Results: Of 70 participants included in the analysis, 57 had classical Hodgkin lymphoma (cHL) and the remainder had B-cell non-Hodgkin lymphoma, multiple myeloma, and myelodysplastic syndrome. Overall, 31 participants (44%) were in remission at first allo-SCT. The median duration of treatment with pembrolizumab was 5.3 months (range, 0.7 to 29.6), and the median time from last dose of pembrolizumab to allo-SCT was 4.6 months (range, 1 to 20). The estimated 6-month cumulative incidence of grade II-IV acute GVHD was 41% (95% confidence interval [CI], 30% to 53%); the estimated 6-month cumulative incidence of grade III-IV acute GVHD was 20% (95% CI, 12% to 30%). The estimated 1-year incidence of chronic GVHD was 19% (95% CI, 11% to 29%). After a median follow-up of 40.1 months, both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 56.8% and the 40-month OS rate was 76.5%. The estimated 40-month cumulative incidence of TRM and relapse was 17% (95% CI, 9% to 27%) and 27% (95% CI, 16% to 38%), respectively. Among participants with cHL (median follow-up, 39.5 months), both the estimated median PFS and median OS after allo-SCT were not reached; the 40-month PFS rate was 59.7% and the 40-month OS rate was 83%. The estimated 40-month cumulative incidence of TRM and relapse in participants with cHL was 12% (95% CI, 5% to 23%) and 23% (95% CI, 12% to 36%), respectively.

Conclusions: Overall, the incidences of acute and chronic GVHD in this cohort were within the expected ranges. PFS and OS outcomes were favorable, and the rates of TRM and relapse were low. These results support allo-SCT as a useful and feasible salvage option after anti-PD-1 therapy.