Sirolimus and Cyclosporine With Post-Transplant Cyclophosphamide or Mycophenolate Mofetil as Graft-Versus-Host Disease Prophylaxis in Unrelated Donor Hematopoietic Cell Transplantation

PURPOSE: To determine whether sirolimus (SIR) and cyclosporine (CSP) combined with post-transplantation cyclophosphamide (PTCy), after nonmyeloablative or reduced-intensity conditioning unrelated donor hematopoietic cell transplantation (HCT), would be more effective than SIR, CSP, and mycophenolate mofetil (MMF) in reducing the risk of chronic graft-versus-host disease (cGVHD) without increasing risk of recurrent malignancy. METHODS: In a Phase II trial of HLA-matched or mismatched unrelated donor mobilized blood HCT (ClinicalTrials.gov identifier: NCT03246906), adults with hematologic malignancies ineligible for myeloablative HCT were randomly assigned 1:1 to GVHD prophylaxis with SIR/CSP/PTCy (50 mg/kg once daily on days +3, +4) or SIR/CSP/MMF. The primary end point was 1-year chronic GVHD-free relapse-free survival (CRFS). RESULTS: = .003). CONCLUSION: After HLA-matched or mismatched unrelated donor mobilized blood HCT, replacing MMF with PTCy, when used in combination with SIR and CSP, significantly reduced risk of cGVHD, without increasing risks of aGVHD or relapse. Thus, the combination of PTCy and SIR/CSP may have synergistic cGVHD-protective effects warranting further study.