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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1409302
This article is part of the Research Topic Immunotherapy in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) View all 6 articles
Anti-PD-1 Combined with Hypomethylating Agent and CAG Regimen Bridging to Allogeneic Hematopoietic Stem Cell Transplantation: A Novel Strategy for Relapsed/ Refractory Acute Myeloid Leukemia
Provisionally accepted- Senior Department of Hematology, the Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China
The prognosis of relapsed/refractory acute myeloid leukemia (r/rAML) is dismal, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is a potential cure. Combining anti-PD-1, hypomethylating agent (HMA), and CAG (cytarabine, aclarubicin/ idarubicin, granulocyte colony-stimulating factor) regimen has showed primary efficacy in r/rAML. However, pre-transplant exposure to anti-PD-1 may lead to severe graft-versus-host disease (GVHD). This preliminary study aimed to evaluate the safety and efficacy of allo-HSCT in r/rAML patients receiving the anti-PD-1+HMA+CAG regimen. Fifteen r/rAML patients (12 related haploidentical donors [HIDs], 2 matched siblings, 1 unrelated donor) received this regimen and subsequent peripheral blood HSCT. Four patients with HIDs received a GVHD prophylaxis regimen consisted of Anti-thymocyte globulin and a reduced-dose of post-transplant cyclophosphamide. The median follow-up was 20.9 months (range, 1.2-34.2). The cumulative incidences of acute GVHD grade 2-4 and grade 3-4 were 40% and 13.3%, respectively. The 2-year incidence of moderate-to-severe chronic GVHD, non-relapse mortality , and relapse were 10%, 22.3%, and 22.5%, respectively. The 2-year overall survival and GVHD-free/relapse-free survival rates were 54% and 48.6%, respectively. No death or relapse was observed in the PTCy group. The anti-PD-1+HMA+CAG regimen bridging to allo-HSCT for r/r AML was tolerable with promising efficacy. GVHD prophylaxis with PTCy for HID-HSCT showed preliminary survival advantage.
Keywords: PD-1 inhibitor, allogeneic hematopoietic stem cell transplantation, relapse /refractory acute myeloid leukemia, Acute graft-versus-host disease, post-HSCT cyclophosphamide
Received: 29 Mar 2024; Accepted: 29 Jul 2024.
Copyright: © 2024 Wang, Wang, Su, Wang, Li, Li, Jing, Xu, Wang, Zheng, Gao, Hu, Gao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liangding Hu, Senior Department of Hematology, the Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China
Xiaoning Gao, Senior Department of Hematology, the Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China
Dai-Hong Liu, Senior Department of Hematology, the Fifth Medical Centre of Chinese PLA General Hospital, Beijing, China
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