Bridging TP53-mutated myelodysplastic syndrome/acute myeloid leukemia to transplant: is venetoclax part of the answer?

Purpose of review TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) remain among the most challenging myeloid malignancies, with poor long-term outcomes despite allogeneic stem cell transplantation (HCT). Venetoclax-based regimens produce encouraging response rates, but their role as optimal pre-transplant therapy for TP53 mutated MDS/AML remains unconfirmed. This review evaluates the rationale and clinical evidence supporting venetoclax as a bridging strategy to HCT. Recent findings Recent studies have refined risk stratification through TP53 allelic-state characterization, demonstrating poor transplant outcomes. Studies show venetoclax-based therapy may induce deeper and faster remissions. A higher proportion of patients who receive venetoclax successfully transition to transplantation. However, higher response rates do not consistently translate into a survival advantage post-transplant. Efforts to study venetoclax regimens in the pre-transplant setting lack stratification by TP53 allelic state or design focus for this subgroup. Summary Current evidence supports venetoclax as an acceptable bridging strategy to accelerate response and cytoreduction for TP53-mutated MDS/AML. There is a limited number of studies of venetoclax-containing regimens specific for transplant eligible patients with TP53 mutated MDS/AML. It is important for future studies to incorporate a standardized TP53 allelic-state assessment, molecular measurable residual disease evaluation, and transplant-specific endpoints.