Journal
TRANSPLANTATION AND CELLULAR THERAPY
Volume 27, Issue 12, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtct.2021.08.022
Keywords
Immunotherapy; Acute myelogenous leukemia; Bone marrow transplantation; Stem cell transplantation; Graft-versus-host disease
Categories
Funding
- Investigator-Initiated Studies Program of Merck, Sharp Dohme Corp
- Duke-UNC Chapel Hill Immunotherapy T32 Training Grant [5T32CA211056-04]
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This study compared the clinical outcomes of AML patients receiving high-dose cytarabine followed by pembrolizumab prior to alloSCT with a historical control group. One-year survival did not significantly differ between the groups, but there was no 100-day mortality in the ICI group, and no increase in the severity of GVHD.
Programmed death 1 (PD-1) is an integral component of acute myelogenous 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. Although allogeneic stem cell transplantation (alloSCT) remains the most established curative treatment for patients with relapsed and refractory AML in complete remission, there are limited data on the clinical outcomes and safety of immune checkpoint inhibitors (ICIs) prior to alloSCT in AML. In the present study, we compared clinical outcomes of 9 patients with AML receiving high-dose cytarabine followed by pembrolizumab in a phase II clinical trial (NCT02768792) prior to alloSCT versus a historical control group of 18 AML patients who underwent alloSCT without prior ICI exposure. The nonparametric Jonckheere-Terpstra test was used to test for a difference in the ordered severity categories of acute graft-versus-host disease (GVHD) within 100 days of transplantation. Time-to-event estimates for overall survival and relapse-free survival were calculated using the Kaplan-Meier method and compared using a log-rank test. One-year survival was not significantly different between the treatment groups (67% versus 78%; P =.34). 100-day mortality was 0% in the ICI group versus 17% in the control group, and there was no increase in grade III-IV acute GVHD in patients treated with pembrolizumab prior to alloSCT. No chronic GVHD was seen in patients treated with pembrolizumab prior to alloSCT and who received post-transplantation cyclophosphamide (PTCy) as part of their conditioning regimen. These findings reinforce the safety and feasibility of ICI therapy prior to alloSCT in patients with AML, and suggest that PTCy may abrogate GVHD risk and severity in patients who receive ICI prior to undergoing alloSCT for AML. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
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