Multicenter phase 3 trial of sitagliptin for acute graft-versus-host disease prevention in alternative donor transplantation

A multicenter phase 3 trial in China evaluated whether addition of sitagliptin to antithymocyte globuline (ATG)-based prophylaxis reduces the incidence of acute graft-versus-host disease (aGVHD) after alternative donor hematopoietic stem-cell transplantation (HSCT). The trial enrolled 190 patients aged 18-60 years with hematologic malignancies who received myeloablative conditioning haploidentical or unrelated donor transplantation. Patient were randomized 1:1 to receive ATG-based prophylaxis (ATG plus calcineurin inhibitor plus methotrecate plus mycophenolate mofetil) with or without sitagliptin (600 mg orally every 12 hourns, days -1 to +14). The primary endpoint was cumulative incidence of grade II-IV aGVHD by day 1000. The median follow-up was 29.8 Months (0.7-41.3). By day 100, the incidence of grade II-IV aGVHD was 14.7% in the sitagliptin group and 31.6% in the control group (sHR 0.41; p=0.005). Reduced grade III-IV (6.3% versus 18.9%; sHR 0.30; p=0.010) and intestinal aGVHD (12.6% versus 29.5%; p=0.004) and superior day 180 GVDH-free, relapse-free survival (86.3% versus 72.6%; HR 0.44; p=0.016) were also observed. No between-group differences were detected in 2-year chronic GVHD, nonrelapse mortality, relaps-free survival, overall survival, or cytomegalovirus/Epstein-Barr virus reactivation. The adverse event profiles were similar. The authors conclude the addition of sitagliptin to ATG-based prophylaxis significantly reduced the incidence of grade II-IV aGVHD (graphical abstract).