Myeloablative vs reduced-intensity conditioning in PTCy-based allogeneic HCT: A CIBMTR analysis.

6563 Background: Post-transplant cyclophosphamide (PTCy) is widely used in matched unrelated and haploidentical HCT. However, the optimal conditioning intensity in the PTCy era remains unclear. This study compared outcomes of myeloablative versus reduced-intensity conditioning in MUD and haploidentical HCT recipients. Methods: This retrospective multicenter study utilized the Center for International Blood and Marrow Transplant Registry (CIBMTR) to analyze patients who underwent HCT and received PTCy, based on the P-6219 dataset by Modi et al. Clinical outcomes were compared between patients who received MAC and RIC. Kaplan–Meier analysis was used to determine mean overall survival (OS) and graft-vs-host disease (GVHD)-free relapse-free survival (GRFS). Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). Statistical analyses were conducted using SPSS, with p-values less than 0.05 considered statistically significant. Results: A total of 5,873 patients were included, comprising 1,973 MUD recipients (797 MAC, 1,176 RIC) and 3,900 haploidentical recipients (1,485 MAC, 2,415 RIC). All patients received PTCy GVHD prophylaxis. Among MUD recipients, MAC was associated with significantly OS compared with RIC, with a mean OS of 27.8 months (95% CI 26.9–28.7) versus 24.8 months (95% CI 24.1–25.6, p<0.001). RIC was associated with a higher risk of mortality compared with MAC (HR 1.45, 95% CI 1.24–1.68, p<0.001). GRFS was also worse with RIC (mean 21.5 months, 95% CI 20.4–22.5 vs 18.3 months, 95% CI 17.4–19.2; HR 1.33, 95% CI 1.17–1.51, p<0.001). There were no significant differences between MAC and RIC in rates of grade 2–4 acute GVHD (HR 1.00, 95% CI 0.85–1.18, p=1.0), grade 3–4 acute GVHD (HR 1.04, 95% CI 0.72–1.51, p=0.84), or moderate/severe chronic GVHD (HR 0.97, 95% CI 0.86–1.08, p=0.59). Among haploidentical recipients, MAC was also associated with improved OS compared with RIC, with a mean OS of 26.1 months (95% CI 25.4–26.8) versus 24.1 months (95% CI 23.6–24.7, p<0.001), and RIC conferred a higher mortality risk (HR 1.29, 95% CI 1.16–1.43, p<0.001). GRFS was superior with MAC (18.4 months, 95% CI 17.6–19.2 vs 16.5 months, 95% CI 15.9–17.2; HR 1.17, 95% CI 1.08–1.27, p<0.001). Rates of grade 2–4 acute GVHD were lower with RIC (HR 0.88, 95% CI 0.78–0.98, p=0.018). Rates of grade 3–4 acute GVHD (HR 1.06, 95% CI 0.85–1.32, p=0.61) and moderate/severe chronic GVHD (HR 0.98, 95% CI 0.90–1.07, p=0.70) were similar between MAC and RIC. Conclusions: MAC was associated with improved OS and GRFS compared with RIC in MUD and haploidentical transplant recipients, with similar rates of severe acute and chronic GVHD. These findings support the use of MAC when patient comorbidities and performance status permit.