Sitagliptin Combined with Tacrolimus and Sirolimus Helps Prevent Acute GVHD

Patients treated with sitagliptin combined with tacrolimus and sirolimus had a low incidence of grade II to IV acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), according to a results of a nonrandomized trial published in the New England Journal of Medicine.

Sitagliptin inhibits dipeptidyl peptidase 4 (DPP-4; also known as CD26), which is expressed on and activates T cells. Previous studies in a mouse model have shown that downregulating CD26 could prevent GVHD but not affect graft-versus-tumor effect.

To determine whether DPP-4 inhibition with sitagliptin can prevent GVHD after allo-HCT, researchers led by Sherif Farag, PhD, MB,BS, FRACP, FRCPA, of the Indiana University School of Medicine, conducted a two-stage, phase 2 trial. They hypothesized that the treatment could lessen incidence of grade II to IV GVHD from 30% to 15% or less by 100 days after allo-HCT.

The study sample included 36 patients with a median age of 46 years (range = 20 to 59) who had received a transplant from a matched related or unrelated donor. They received conditioning treatment with tacrolimus and sirolimus before transplantation. In addition, they received oral sitagliptin (600 mg every 12 hours starting the day before transplantation until day 14 after transplantation).

Among the 36 patients, the rate of GVHD-free, relapse-free survival was 46%. No patients died at the one-year mark. Overall, 5% developed acute GVHD by day 100. Five percent had grade II to IV (95% confidence interval [CI], 1 to 16), and 3% had grade III or IV GVHD (95% CI, 0 to 12). At one year, the cumulative incidence of relapse was 26% (95% CI, 13 to 41), and the cumulative incidence of chronic GVHD was 37% (95% CI, 22 to 53). The toxicity profile was similar to general populations of patients undergoing allo-HCT, the researchers noted.

The authors concluded that sitagliptin in combination with tacrolimus and sirolimus shows promise in lowering rates of GVHD after allo-HCT and should be examined further for this indication.