Emerging venetoclax plus hypomethylating agent-based triplet regimens in newly diagnosed acute myeloid leukemia: updates from the 2025 ASH Annual Meeting

Venetoclax (VEN) combined with a hypomethylating agent (HMA) has become a standard-of-care frontline therapy for unfit patients with newly diagnosed acute myeloid leukemia (ND AML). The VIALE-A trial established the clinical benefit of VEN plus azacitidine (AZA), with a composite complete remission rate (CRc) of 66.4% and a median overall survival (OS) of 14.7 months. Nevertheless, remission durability remains heterogeneous, and the regimen is non-curative for many patients. Improving remission rates and long-term survival therefore remains an urgent unmet clinical need. VEN/HMA-based triplet regimens incorporating targeted agents are emerging as promising strategies in ND AML, particularly FLT3 inhibitor-based combinations reported at the 2025 American Society of Hematology (ASH) Annual Meeting. Notably, longer-term follow-up data from a study of gilteritinib plus VEN/AZA in patients with ND FLT3-mutated AML showed a median OS of 29.7 months. Additional VEN/HMA-based strategies, including combinations with menin inhibitors and other novel agents, are also being investigated. Here, we provide an overview of the latest clinical updates on VEN/HMA-based triplet regimens in ND AML presented at the 2025 ASH Annual Meeting.