Among patients receiving myeloablative allogeneic hematopoietic stem cell transplantation (HSCT), sitagliptin plus tacrolimus and sirolimus may lead to low incidence of grade 2 to 4 acute graft-vs-host disease (GVHD), according to research published in The New England Journal of Medicine.
Acute GVHD is a leading cause of death after HSCT; by 100 days after transplantation, grade 2 to 4 disease occurs in 34% to 51% of patients, even when receiving standard prophylaxis regimens.
Dipeptidyl peptidase 4 (DPP-4; also known as CD26) is thought to be involved in the development of GVHD. Previous research suggests that sitagliptin, a selective inhibitor of DPP-4, may reduce the incidence of GVHD after engraftment of cord-blood transplants.
In this nonrandomized phase 2 clinical trial (ClinicalTrials.gov Identifier: NCT02683525), investigators sought to test whether sitagliptin with tacrolimus and sirolimus would reduce the incidence of acute GVHD by day 100 after HSCT.
Of the 37 patients enrolled in the trial, 36 patients (median age, 46 years) were available for evaluation. Following myeloablative conditioning, patients received mobilized peripheral-blood stem cell transplants. Sitagliptin (600 mg) was administered orally every 12 hours from 1 day before to 14 days after transplantation.
By day 100, acute GVHD occurred in 2 patients; 1 patient with grade 2 and 1 patient with grade 4 GVHD. Sitagliptin had a tolerable side effect profile, and the researchers noted no toxic effects attributed to the drug. Of the cohort, 28 patients received 80% or more of the 32 planned doses of sitagliptin.
The median follow-up was 700 days; 9 patients had a relapse at a median of 243 days after transplantation. The 1-year cumulative incidence of relapse was 26%. Of the 34 patients who survived without relapse for more than 100 days, 15 patients developed chronic GVHD, for a total 1-year cumulative incidence of 37%.
The authors concluded that sitagliptin plus sirolimus and tacrolimus is safe and feasible for patients undergoing HSCT after myeloablative conditioning. The prophylactic regimen led to low incidence of acute GVHD with an acceptable side effect profile. The trial results also show that DPP-4 is a viable target to help prevent acute GVHD. The incidence of acute GVHD in this trial was lower than in trials testing sirolimus and tacrolimus alone. However, this trial was small and did not contain a control group.
Sitagliptin is an attractive candidate given early results, availability and low cost, but further randomized trials are needed to confirm its efficacy.
Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Farag SS, Abu Zaid M, Schwartz JE, et al. Dipeptidyl peptidase 4 inhibition for prophylaxis of acute graft-versus-host disease. N Engl J Med. 2021;384(1):11-19. doi:10.1056/NEJMoa2027372