Sitagliptin for Acute Graft-Versus-Host Disease Prevention in Alternative Donor Transplantation: A Randomized Phase III Trial
In brief
Sitagliptin halved moderate-to-severe graft-versus-host disease by day 100
In a randomized trial of 190 adults receiving alternative-donor stem-cell transplants, adding sitagliptin to standard prevention reduced grade 2 to 4 acute graft-versus-host disease from 31.6% to 14.7% by day 100. Severe and intestinal disease also fell, but those findings were exploratory, and the trial found no improvement in long-term survival or relapse outcomes.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 6 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Man Qiao, Biqi Zhou, Yiyin Chen, Huiying Qiu, Shengli Xue, Ying Wang, et al.
- PMID
- 42837636
- DOI
- 10.1200/JCO-26-00670
Why clinicians should know about it
- Picked for Hematology (paper of the day, 7 October 2026): Sitagliptin reduces acute GVHD after HSCT
- Picked for Oncology and Radiation Oncology (paper of the day, 7 October 2026): Sitagliptin reduces grade II‑IV aGVHD in ATG‑based HSCT prophylaxis
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.