Phase II Study of Posttransplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After HLA-Mismatched...

Posttransplant cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) improves outcomes in recipients of HLA mismatched unrelated donor (MMUD) allogeneic hematopoietic cell transplantation (allo HCT). Outcomes of MMUD HCT using PTCy in patients requiring reduced intensity or non-myeloablative conditioning (RIC/NMA) are not well described. The Phase II, prospective, ACCESS trial sought to evaluate PTCy-based GVHD prophylaxis in adult recipients of MMUD using peripheral blood stem cell allografts. Here, we report combined results of RIC/NMA recipients treated in the initial study (N = 70) and a planned expansion cohort (N = 123). The number of centers participating in the expansion protocol was 33 compared to 13 in the initial study. Median participant age was 65.0 (range: 22.9-78.9) and the HCT comorbidity index was high-risk (≥ 3) in 65 (33.7%). Donor HLA matching was < 7/8 in 62 (32.1%) participants. One-year survival was 79.6% (95% confidence interval: 73.2-84.7) and was similar between HLA 7/8- and HLA < 7/8-matched donor recipients. Survival was similar between participants in the initial study (78.6%) and the expansion cohort (80.3%) indicating generalizability of this strategy. One-year incidence of severe infection (Grade 3-5) was 39% (32%-46.9%). The 1-year incidence of non-relapse mortality and relapse estimates were 12.5% (8.3%-17.6%) and 17.3% (12.3%-23%), respectively. MMUD with PTCy-based GVHD prophylaxis and RIC/NMA conditioning was safe and effective to facilitate HCT. Outcomes were similar in the expansion cohort that enrolled from a greater number of centers. Post-HCT infections were prevalent.