A Calcineurin Inhibitor Free Graft Versus Host Disease Prophylaxis for Patients Undergoing Matched Related and Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplant

Abstract

Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI)-based graft versus host disease (GVHD) prophylaxis has been associated with lower rates of acute and chronic GVHD compared with the traditional prophylaxis of CNI and methotrexate (MTX) in matched related donor (MRD) and matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT). The combination of PTCy with sirolimus (PTCy-Siro) as CNI-free GVHD prophylaxis has shown promising results, with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15% to 27% and 20% to 27%, respectively, in patients undergoing MRD, MUD, and haploidentical allo-HCT. We report a single-center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy-Siro with those receiving the standard GVHD prophylaxis of tacrolimus and methotrexate (Tac-MTX). One hundred and sixteen consecutive patients who had undergone an MRD or MUD allo-HCT between January 2018 and January 2021 and received either PTCy-Siro (n = 29) or Tac-MTX (n = 87) as GVHD prophylaxis regimens were eligible for inclusion. Patients receiving PTCy-Siro had a significantly shorter median time to immunosuppression withdrawal than patients receiving Tac-MTX (138 days [range, 37 to 312 days] versus 232 days [range, 66 to 1120 days]; P < .001). There was no significant difference between the 2 arms in the incidence of grade II-IV acute GVHD, grade III-IV acute GVHD, steroid-refractory acute GVHD, or clinical infections. At a median follow-up of 1.1 years (range, 0 to 1.8 years), patients receiving PTCy-Siro were significantly less likely to have chronic GVHD, with 2-year freedom from GVHD of 75% (95% confidence interval [CI], 58% to 98%) versus 20% (95% CI, 10% to 40%) for those receiving Tac-MTX (P = .005).