Relapse Incidence Post Unrelated Allogeneic Stem Cell Transplantation with Post-Transplant Cyclophosphamide (PTCy) in Patients with Acute Myeloid Leukemia: A Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Background Post-transplant cyclophosphamide (PTCy) reduces chronic (c) graft-versus-host disease (GVHD) and thus may suppresses the graft-versus-leukemia (GVL) effect leading to increased relapse (RI). Methods Study aim was to compare RI post 9-10/10 unrelated donor transplantations (UD-HSCT) with PTCy vs no PTCy (in vivo T-cell depletion or calcineurin inhibitor-based) GVHD prophylaxis, in adult patients (pts) with AML in CR1 transplanted between 2014 and 2021 with peripheral blood grafts. Statistical tests included a multivariate analysis (MVA) using a Cox proportional-hazards regression model for main outcomes. Results In total, 7049 pts were included: 707 received PTCy, and 6342 did not (no PTCy). Median follow-up was 1.9 (range, 1.7-2.1) and 2.9 (range, 2.8-3) years(y). Outcomes were censored at 2 y. The pts in the PTCY group were younger, median age was 52.7 (range, 18-77.5) vs 56.6 (range, 18-80.3) y in the no PTCy group (p<0.001). Cytogenetic risk (MRC classification) was favorable, intermediate, and adverse in 5.6% vs 5.1%; 69.2% vs 67.8%, and 25.2% vs 27.1% of the pts, respectively (p=0.54) (missing data-1196 (17%) pts). There were more HLA 9/10 donors in the PTCy group than the no PTCy group with 33.8% vs 16.4% (p<0.001). More pts in the PTCy group than the no PTCy group received myeloablative conditioning (MAC), with 61.7% vs 50.2% (p<0.001). In the no PTCy group, 87.7% of pts received in vivo T-cell depletion.Day 30 neutrophil engraftment was achieved in 93.8% vs 97.6% of the pts in the PTCy and no PTCy groups. In the MVA, RI was not significantly different in the PTCy compared to the no PTCy group, with a hazard ratio (HR) of 1.11 (95% CI 0.9-1.37) (p=0.31) (Figure). Relapse was the main cause of death in both groups, 58.8% vs 54.3% of the pts that died. Day 180 acute (a) GVHD (grades II-IV and severe grades III-IV) were significantly lower with PTCy compared to the no PTCy group, with HR of 0.74 (95% CI 0.59-0.92, p=0.007) and HR=0.56 (95% CI 0.38-0.83, p=0.004), as were 2-y cGVHD (total and extensive) with HRs of 0.5 (95% CI 0.41-0.62, p=0.001) and HR=0.31 (95% CI 0.22-0.42, p=0.001). NRM was significantly lower with PTCy compared to the no PTCy group with an HR of 0.67 (95% CI 0.5-0.91, p=0.007). The main causes of NRM were infections and GVHD. GRFS was higher in the PTCY vs the no PTCy group, with a HR=0.69 (95% CI 0.59-0.81, p=0.001). LFS, and OS did not differ significantly between the groups, with HRs of 0.93 (95% CI 0.78-1.1, p=0.39) and HR=0.93 (95% CI 0.77-1.12, p=0.45), respectively (Figure). Conclusions In this registry-based, retrospective analysis of UD-HSCT with PTCy versus no PTCy- in pts with AML in CR1, we observed non-significantly different 2-y RI, OS, and LFS. Incidence of GVHD and NRM were significantly lower with PTCy resulting in significantly better GRFS with PTCy compared to no PTCy anti-GVHD prophylaxis. Clinically, these results do not support PTCy negating the GVL effect in UD-HSCT.