Safety and Efficacy of Pembrolizumab Prior to Allogeneic Stem Cell Transplantation for Acute Myelogenous Leukemia.

Abstract Background : Programmed death-1 (PD-1) is an integral component of acute myeloid leukemia (AML) immune evasion, chemotherapy resistance, and disease progression. PD-1 inhibitors are being investigated as treatment for AML in combination with hypomethylating agents and cytotoxic chemotherapy with encouraging findings. Objective : Although allogeneic stem cell transplant (alloSCT) remains the most established curative treatment for relapsed and refractory AML patients in complete remission, there are limited data on the clinical outcomes and safety of immune checkpoint inhibitors (ICIs) prior to alloSCT in AML. Study Design : We compared clinical outcomes of AML patients receiving high-dose cytarabine followed by pembrolizumab (n=8) in a phase II clinical trial (NCT02768792) prior to alloSCT versus a historical control group of AML patients who received alloSCT without prior ICI exposure (n=18). The nonparametric Jonckheere–Terpstra test was used to test for a difference in the ordered severity categories of aGVHD within 100 days of transplant. The time-to-event estimates for OS and relapse-free survival were calculated using the Kaplan–Meier method and compared using a log rank test. Results : One-year survival was not significantly different between both treatment groups (67% versus 78%, p = 0.34). 100-day mortality was 0% in the pembrolizumab cohort versus 17% in control group, and there was no increase in grade III-IV acute graft-versus-host disease in patients treated with pembrolizumab prior to alloSCT. No chronic graft-versus-host disease was seen in patients treated with pembrolizumab prior to alloSCT and who received post-transplant cyclophosphamide as part of their conditioning regimen. Conclusion : These findings reinforce the safety and feasibility of ICI prior to alloSCT in AML. These results suggest post-transplant cyclophosphamide may abrogate GVHD risk and severity in patients who receive ICI prior to alloSCT in AML.