PTCy-Based versus ATG-Based GVHD Prophylaxis in Mismatched Unrelated Donor HCT: A Secondary Analysis of CIBMTR Data

The optimal graft-versus-host disease (GVHD) prophylaxis strategy for 7/8 human leukocyte antigen (HLA)-mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) has not been established. We performed a secondary analysis of a publicly available Center for International Blood and Marrow Transplant Research (CIBMTR) dataset (P-5891) including adults undergoing first 7/8 MMUD HCT between 2017 and 2021. Patients were stratified by GVHD prophylaxis: anti-thymocyte globulin (ATG) with calcineurin inhibitor (CNI) and methotrexate (n = 221), or post-transplant cyclophosphamide (PTCy) with CNI and mycophenolate mofetil (n = 613). PTCy was associated with lower grade II-IV acute GVHD (30.7% versus 50.3%; P < .001) and grade III-IV acute GVHD (7.7% versus 23.8%; P < .001). Nonrelapse mortality (NRM) at 24 months was 17.2% versus 35.1% (P < .001). Rates of moderate-severe chronic GVHD and relapse were comparable. GVHD-free/relapse-free survival (GRFS) at 24 months was 44.9% versus 26.7% (P < .001), and overall survival (OS) at 24 months was 63.9% versus 46.6% (P < .001). On multivariable analysis, PTCy was independently associated with improved GRFS (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.48-0.72; P < .001), lower NRM (HR 0.44, 95% CI 0.32-0.60; P < .001), and improved OS (HR 0.60, 95% CI 0.44-0.72; P < .001), without an increase in relapse risk (HR 1.07, 95% CI 0.77-1.48; P = .68). In this registry-based analysis, PTCy-based prophylaxis was associated with improved OS, NRM, and GRFS compared with ATG-based prophylaxis in 7/8 MMUD HCT. Prospective studies comparing these strategies specifically in MMUD recipients are needed to confirm these findings.