Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial
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.
// Source
Authors: Man Qiao, Biqi Zhou, Y H 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, 戴海萍, Tao You, Xiebing Bao, Zaixiang Tang, Xiaofei Yang, Robert Zeiser, Suning Chen, Depei Wu, Yang Y. Xu
Institutions: Shenzhen Second People's Hospital, Soochow University, Nanjing Medical University, German Cancer Research Center, Southern Medical University Shenzhen Hospital, University of Freiburg, First Affiliated Hospital of Soochow University, University Medical Center Freiburg, Southern University of Science and Technology, Second People’s Hospital of Huai’an, Suzhou Yongding Hospital