Diabetes Drug Shines as GVHD Prophylaxis- NEJM
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Patients undergoing matched allogeneic stem-cell transplantation (SCT) had a low incidence of graft-versus-host disease (GVHD) with the addition of the diabetes drug sitagliptin (Januvia) to standard prophylaxis, a small prospective study showed.

Dipeptidyl 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.

Researchers 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.

Results:
-- A 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%, and the incidence of grade III or IV GVHD was 3%.

-- Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% and 37% respectively.

-- GVHD-free, relapse-free survival was 46% at 1 year.

-- Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation.

Conclusively, in 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.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2027372
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