抗PD-1结合甲基化剂和CAG方案桥接到同种异体造血干细胞移植：复发/难治性急性髓性白血病的新型策略
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
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Yu-Xin Wang, An Wang, Yong-Feng Su, Jun Wang, Yu-Hang Li, Fei Li, Yu Jing, Lei Xu, Yi-Zhi Wang, Xuan Zheng, Chun-Ji Gao, Liang-Ding Hu, Xiao-Ning Gao, Dai-Hong Liu
摘要
复发/难治性急性髓样白血病（R/RAML）的预后令人沮丧，同种异体造血干细胞移植（Allo-HSCT）是一种潜在的治疗方法。结合抗PD-1，低甲基化剂（HMA）和CAG（细胞甲滨，阿卡鲁比辛/idarubicin，粒细胞刺激因子）治疗方案在R/RAML中显示出一级疗效。但是，移植前暴露于抗PD-1可能会导致严重的移植物抗宿主病（GVHD）。这项初步研究旨在评估接受抗PD-1+HMA+CAG方案的R/RAML患者的安全性和有效性。fift15例R/RAML患者（12名相关的单身供体[HIDS]，2名与此相匹配的捐助者，1名不相关的捐助者接收了该治疗方案，并接收了与随后的血液中的hs gcthf。预防疗法由抗心理细胞球蛋白和减少剂量移植后环磷酰胺组成。中位随访时间为20.9个月（范围为1.2-34.2）。急性GVHD 2-4级和3-4级的累积发生率分别为40％和13.3％。中度至重度慢性GVHD，非释放死亡率和复发的2年发病率分别为10％，22.3％和22.5％。 2年的总生存期和无GVHD/无复发生存率分别为54％和48.6％。在PTCY组中未观察到死亡或复发。抗PD-1+HMA+CAG方案为R/R AML桥接到Allo-HSCT上，具有有希望的功效。用PTCY进行HID-HSCT的GVHD预防显示出初步的生存优势。
Abstract
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.