Triplet regimens for all: genomically agnostic approaches to improve on HMA + VEN in AML?
- Details
- Publication Year 2025-12-05,Volume 2025,Issue #1,Page 607-613
- Journal Title
- Hematology, ASH Education Program
- Publication Type
- Review
- Abstract
- Combined hypomethylating agent (HMA) plus venetoclax (Ven) therapy enables most older patients with acute myeloid leukemia (AML) to achieve clinical remission. Key objectives are now aimed at developing new triplet combinations to circumvent mechanisms of resistance and extend remission longevity and, by extension, survival. Genomically agnostic approaches combine hypomethylating agents and venetoclax (HMA-Ven) with novel agents directed at oncogenic pathways critical for leukemic cell survival, proliferation, metabolism, or differentiation. Challenges faced in the development of new HMA-Ven triplets include competition from targeted inhibitors, biological heterogeneity of AML, potential for additive toxicity, reduced efficacy from modifications to the HMA-Ven backbone, and the higher bar for success in older AML beyond the current standard of care.
- Keywords
- Humans; *Leukemia, Myeloid, Acute/drug therapy/genetics/metabolism; *Bridged Bicyclo Compounds, Heterocyclic/therapeutic use; *Sulfonamides/therapeutic use; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Aged
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1182/hematology.2025000756
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-01-23 11:58:23
Last Modified: 2026-01-23 12:00:54