Venetoclax-enhanced reduced-intensity conditioning in older patients aged ≥55 years with high-risk myeloid malignancies undergoing allogeneic peripheral blood stem cell transplantation: A phase II study.

Reduced-intensity conditioning (RIC) is associated with a high relapse rate in high-risk acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). It remains unclear whether venetoclax, an anti-leukaemic agent, can enhance RIC efficacy. A prospective, single-arm, phase 2 trial enrolled patients with high-risk AML or MDS, aged ≥55 years, who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT). All patients received venetoclax-enhanced RIC (VEN-RIC), comprising venetoclax, busulfan, fludarabine, cytarabine and low-dose total body irradiation (TBI). Fifty patients (median age 62) were enrolled. At a median follow-up of 14.9 months, the 1-year progression-free survival (PFS) was 72.5%, while 1-year overall survival (OS) and graft-versus-host disease/relapse-free survival (GVHD/GRFS) were 73.8% and 56.9% respectively. The 1-year cumulative incidence of relapse and non-relapse mortality were 16.8% and 10.6%. The 180-day cumulative incidence of acute GVHD was 22.9%, while the 1-year cumulative incidence of chronic GVHD was 25.8%. Multivariable analysis showed TP53 mutation was the strongest predictor of worse OS, PFS and GRFS, as well as higher relapse. We conclude that VEN-RIC is feasible and associated with encouraging survival and a manageable safety profile, warranting confirmation in randomized studies.