• Sherif S Farag, Mohammad Abu Zaid, Jennifer E Schwartz, Teresa C Thakrar, Ann J Blakley, Rafat Abonour, Michael J Robertson, Hal E Broxmeyer, and Shuhong Zhang.
• From the Indiana University School of Medicine (S.S.F., M.A.Z., J.E.S., R.A., M.J.R., H.E.B., S.Z.), Indiana University Health (S.S.F., M.A.Z., J.E.S., T.C.T., R.A., M.J.R.), and Indiana University Simon Comprehensive Cancer Center (S.S.F., A.J.B., H.E.B.) - all in Indianapolis.
• N. Engl. J. Med. 2021 Jan 7; 384 (1): 11-19.

BackgroundDipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known.MethodsWe conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation.ResultsA total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation.ConclusionsIn this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).Copyright © 2021 Massachusetts Medical Society.

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