Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial

IF 44.7 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2026-10-06 DOI:10.1200/jco-26-00670

Man Qiao,Biqi Zhou,Yiyin Chen,Huiying Qiu,Shengli Xue,Ying Wang,Yue Han,Yanming Zhang,Kourong Miao,Jihao Zhou,Miao Miao,Xiao Ma,XiaoJin Wu,Xuefeng He,Xiaohui Hu,Mingming Hu,Han Zhu,Rongxian Wang,Haiping Dai,Tao You,Xiebing Bao,Zaixiang Tang,Xiaofei Yang,Robert Zeiser,Suning Chen,Depei Wu,Yang Xu

{"title":"Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial","authors":"Man Qiao,Biqi Zhou,Yiyin Chen,Huiying Qiu,Shengli Xue,Ying Wang,Yue Han,Yanming Zhang,Kourong Miao,Jihao Zhou,Miao Miao,Xiao Ma,XiaoJin Wu,Xuefeng He,Xiaohui Hu,Mingming Hu,Han Zhu,Rongxian Wang,Haiping Dai,Tao You,Xiebing Bao,Zaixiang Tang,Xiaofei Yang,Robert Zeiser,Suning Chen,Depei Wu,Yang Xu","doi":"10.1200/jco-26-00670","DOIUrl":null,"url":null,"abstract":"PURPOSE This trial evaluated whether the addition of sitagliptin to antithymocyte globulin (ATG)–based prophylaxis reduces the incidence of acute graft-versus-host disease (aGVHD) after alternative donor hematopoietic stem-cell transplantation. METHODS This prospective, multicenter, open-label, randomized trial enrolled patients age 18-60 years with hematologic malignancies who received myeloablative conditioning haploidentical or unrelated donor transplantation. Participants were randomly assigned in a 1:1 ratio to ATG-based prophylaxis (ATG + calcineurin inhibitor + methotrexate + mycophenolate mofetil) with or without sitagliptin (600 mg orally once every 12 hours, days –1 to +14). The primary end point was the cumulative incidence of grade Ⅱ-Ⅳ aGVHD by day +100. RESULTS From December 22, 2021, to June 16, 2023, 190 of the 251 screened patients were enrolled, with a median follow-up of 29.8 (0.7-41.3) months. The sitagliptin group had a significantly lower incidence of grade Ⅱ-Ⅳ aGVHD on day +100 (14.7% v 31.6%; subdistribution hazard ratio [sHR] = 0.41; P = .005). Reduced grade Ⅲ-Ⅳ (6.3% v 18.9%; sHR = 0.30; P = .010) and intestinal aGVHD (12.6% v 29.5%; P = .004) and superior day +180 GVHD-free, relapse-free survival (GRFS; 86.3% v 72.6%; HR = 0.44; P = .016) were also observed. No between-group disparities were detected in 2-year chronic GVHD, nonrelapse mortality, relapse-free/overall survival, or cytomegalovirus/Epstein-Barr virus reactivation; the adverse event profiles were similar. CONCLUSION In this randomized trial, adjunct sitagliptin to ATG-containing prophylaxis significantly reduced the incidence of grade Ⅱ-Ⅳ aGVHD. Reductions in severe and intestinal aGVHD, as well as improved day +180 GRFS, were exploratory observations; no significant benefits were detected for long-term GRFS, overall survival, or RFS, and treatment did not alter the engraftment, relapse, or infection risk.","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":"18 1","pages":""},"PeriodicalIF":44.7000,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/jco-26-00670","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

PURPOSE This trial evaluated whether the addition of sitagliptin to antithymocyte globulin (ATG)–based prophylaxis reduces the incidence of acute graft-versus-host disease (aGVHD) after alternative donor hematopoietic stem-cell transplantation. METHODS This prospective, multicenter, open-label, randomized trial enrolled patients age 18-60 years with hematologic malignancies who received myeloablative conditioning haploidentical or unrelated donor transplantation. Participants were randomly assigned in a 1:1 ratio to ATG-based prophylaxis (ATG + calcineurin inhibitor + methotrexate + mycophenolate mofetil) with or without sitagliptin (600 mg orally once every 12 hours, days –1 to +14). The primary end point was the cumulative incidence of grade Ⅱ-Ⅳ aGVHD by day +100. RESULTS From December 22, 2021, to June 16, 2023, 190 of the 251 screened patients were enrolled, with a median follow-up of 29.8 (0.7-41.3) months. The sitagliptin group had a significantly lower incidence of grade Ⅱ-Ⅳ aGVHD on day +100 (14.7% v 31.6%; subdistribution hazard ratio [sHR] = 0.41; P = .005). Reduced grade Ⅲ-Ⅳ (6.3% v 18.9%; sHR = 0.30; P = .010) and intestinal aGVHD (12.6% v 29.5%; P = .004) and superior day +180 GVHD-free, relapse-free survival (GRFS; 86.3% v 72.6%; HR = 0.44; P = .016) were also observed. No between-group disparities were detected in 2-year chronic GVHD, nonrelapse mortality, relapse-free/overall survival, or cytomegalovirus/Epstein-Barr virus reactivation; the adverse event profiles were similar. CONCLUSION In this randomized trial, adjunct sitagliptin to ATG-containing prophylaxis significantly reduced the incidence of grade Ⅱ-Ⅳ aGVHD. Reductions in severe and intestinal aGVHD, as well as improved day +180 GRFS, were exploratory observations; no significant benefits were detected for long-term GRFS, overall survival, or RFS, and treatment did not alter the engraftment, relapse, or infection risk.

查看原文本刊更多论文

西格列汀用于替代供体移植预防急性移植物抗宿主病：一项随机III期试验

目的：本试验评估西格列汀加入抗胸腺细胞球蛋白（ATG）预防是否能降低替代供体造血干细胞移植后急性移植物抗宿主病（aGVHD）的发生率。方法：这项前瞻性、多中心、开放标签、随机试验纳入了年龄在18-60岁的恶性血液病患者，这些患者接受了清髓调节单倍体或非亲属供体移植。参与者以1:1的比例随机分配到以ATG为基础的预防（ATG +钙调磷酸酶抑制剂+甲氨蝶呤+霉酚酸酯），有或没有西格列汀（600毫克，每12小时口服一次，第1天至第14天）。主要终点是第100天Ⅱ-Ⅳ级aGVHD的累积发病率。结果从2021年12月22日至2023年6月16日，251例筛查患者中有190例入组，中位随访时间为29.8（0.7-41.3）个月。西格列汀组在第100天Ⅱ-Ⅳ级aGVHD发生率显著降低（14.7% vs 31.6%；亚分布风险比[sHR] = 0.41; P = 0.005）。患者的分级降低Ⅲ-Ⅳ（6.3% v 18.9%; sHR = 0.30; P = 0.010），肠道aGVHD (12.6% v 29.5%; P = 0.004)，无gvhd、无复发生存（GRFS; 86.3% v 72.6%; HR = 0.44; P = 0.016）。在2年慢性GVHD、非复发死亡率、无复发/总生存率或巨细胞病毒/ eb病毒再激活方面，组间未发现差异；不良事件概况相似。结论：在这项随机试验中，西格列汀辅助含atg预防可显著降低Ⅱ-Ⅳ级aGVHD的发生率。严重和肠道aGVHD的减少，以及day +180 GRFS的改善是探索性观察；在长期GRFS、总生存期或RFS方面没有发现明显的益处，治疗也没有改变植入、复发或感染的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.