Sitagliptin Reduced Acute GVHD After Alternative Donor Transplantation in Randomized Trial

A prospective, multicenter, open-label phase III trial evaluated adjunctive sitagliptin for acute graft-versus-host disease (aGVHD) prevention in 190 adults aged 18–60 years with hematologic malignancies undergoing myeloablative haploidentical or unrelated donor transplantation. Patients were randomized to antithymocyte globulin, a calcineurin inhibitor, methotrexate, and mycophenolate mofetil, with or without sitagliptin 600 mg orally every 12 hours from day −1 through day +14. The primary endpoint was cumulative grade II–IV aGVHD incidence by day +100.

Grade II–IV aGVHD occurred in 14.7% of the sitagliptin group versus 31.6% of controls (subdistribution hazard ratio, 0.41; P=.005). Grade III–IV aGVHD rates were 6.3% versus 18.9%, and intestinal aGVHD rates were 12.6% versus 29.5%. Day +180 GVHD-free, relapse-free survival was 86.3% versus 72.6% (hazard ratio, 0.44; P=.016). Median follow-up was 29.8 months.

The findings support reduced early aGVHD with adjunctive sitagliptin in this transplant setting, but severe and intestinal aGVHD reductions and improved early composite survival were exploratory observations. No significant long-term survival benefits were detected, and adverse event profiles were similar. The open-label design and restriction to adults aged 18–60 receiving myeloablative transplantation limit interpretation and generalizability. This report is based on the journal abstract; full text was unavailable.