FluBu2 and FluMel with and without PTCY: Comparative effectiveness and safety in allogeneic stem transplantation for adults with myeloid malignancies.

e18563 Background: Reduced-intensity conditioning regimens, such as fludarabine with 2 days of busulfan (FluBu2) or fludarabine with melphalan (FluMel), are increasingly being utilized in adult allogeneic hematopoietic cell transplants (allo-HCT). While post-transplantation cyclophosphamide (PTCy) is widely used for GVHD prophylaxis, the optimal regimen when combined with PTCy remains undetermined. This study compares outcomes in four conditioning regiments: FluBu2, FluMel, FluBu2+PTCy, and FluMel+PTCy. Methods: This retrospective study followed patients undergoing allo-HCT for myeloid malignancy (AML/MDS/CML) at our center between April 2017 and March 2024, classified them by their respective conditioning regiment, and tracked relevant clinical endpoints including overall survival (OS), relapse, and non-relapse mortality (NRM). Results: 166 patients were analyzed: FluBu2 (n = 70), FluMel (n = 28), FluBu2+PTCy (n = 40), and FluMel+PTCy (n = 28). In the FluBu2 and FluMel groups, all patients underwent HLA-matched allo-HCT. Compared to the FluBu2+PTCy, the FluBu2 group had more elderly patients (p = 0.04) and trended towards more AML (p = 0.06), lower KPS (p = 0.08), and higher HCT-CI scores (p = 0.07). The FluBu2+PTCy group had more patients in non-remission (p = 0.01) and higher HCT-CI scores (p = 0.09) than FluMel+PTCy. The 3-year relapse rates were FluBu2: 42.1%, FluMel: 19.6%, FluBu2+PTCy: 24.7%, and FluMel+PTCy: 10.2%, with a significantly higher relapse rate in the FluBu2 group (p = 0.008). No significant differences in NRM were observed among the four groups (3-year NRM: FluBu2 19.0%, FluMel 20.1%, FluBu2+PTCy 13.5%, FluMel+PTCy 8.3%, p = 0.81). The 3-year OS rates were FluBu2: 37.0%, FluMel: 59.1%, FluBu2+PTCy: 62.9%, and FluMel+PTCy: 81.8%, with a significantly lower OS in the FluBu2 group (p = 0.04). In multivariate analysis, FluBu2 was identified as a significant risk factor for relapse and overall mortality. FluBu2 remained a significant risk factor for overall mortality in multivariate analysis, even when compared with FluBu2+PTCy (HR 1.94, p = 0.03). On the other hand, no statistically significant differences were observed between the FluBu2+PTCy and FluMel+PTCy for relapse, NRM, or OS. All patients in the FluMel and FluMel+PTCy groups achieved full donor chimerism (>95% donor chimerism, FDC) at Day 30 post-transplantation. In the FluBu2 regimen, regardless of PTCy use, fewer patients achieved FDC for both total cells and T cells compared to the FluMel regimen (p<0.01). Conclusions: FluBu2 is associated with higher relapse rates, likely due to lower intensity, but adding PTCy may mitigate risk of relapse. The FluMel regimen, when combined with PTCy, appears safe and effective without increasing NRM. Further studies are needed to validate these findings and inform regimen selection.