Extended Versus Standard Hypomethylating Agent Dosing in Combination With Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia.

Authors

• Georgio Medawar
• Jean-Sebastien Anoma
• Elizabeth Hill
• Serena Tharakan
• Dahniel L Sastow
• Vincent Lok
• Su Bin Hahn
• Sarah Chen
• Thomas Kehoe
• Chidambaram Ramasamy
• Julian Guetta-Weiss
• Kapil Meleveedu
• Chenyu Lin
• David M Swoboda
• Douglas Tremblay
• Alexander Coltoff

Publication/Presentation Date

5-1-2026

Abstract

The optimal duration of hypomethylating agent (HMA) therapy combined with venetoclax (Ven) in newly diagnosed acute myeloid leukemia (ND-AML) remains uncertain. Standard of care (SOC) uses 5-day decitabine (Dec-5) or 7-day azacitidine (Aza-7), while extended HMA regimens (e.g., 10-day decitabine [Dec-10] during cycle 1) have also been explored, although direct comparative data between these approaches are limited. We conducted a large retrospective analysis of 335 patients with ND-AML treated at five US centers with Dec-10/Ven (n = 102) or SOC HMA/Ven (n = 233). Baseline characteristics were largely balanced, though the Dec-10 group had more treated secondary AML, and the SOC group had more intermediate risk by ELN-2024. Dec-10/Ven exhibited significantly higher composite complete remission rates (CRc) (82% vs. 70%, p = 0.029), but similar measurable residual disease (MRD) negativity rates (27% vs. 25%, p = 0.6) at best response. Median overall survival (OS) was significantly longer for Dec-10/Ven, 22.2 versus 9.1 months for SOC (p <  0.001). Transplantation was more frequent following Dec-10/Ven (25% vs. 6%, p <  0.001). The 30-day and 60-day mortality rates were similar (7% vs. 11%, p = 0.4; 13% vs. 23%, p = 0.1). On multivariable analysis, the Dec-10 regimen, de novo AML, non-complex karyotype, and IDH2 mutation were associated with a significantly lower risk of death. Our findings suggest that Dec-10/Ven may lead to improved transplant rates and survival, providing valuable real-world support for this intensified approach in appropriate patients. Prospective randomized evaluation is warranted.

Volume

44

Issue

3

First Page

70198

Last Page

70198

ISSN

1099-1069

Published In/Presented At

Medawar, G., Anoma, J. S., Hill, E., Tharakan, S., Sastow, D. L., Lok, V., Hahn, S. B., Chen, S., Kehoe, T., Ramasamy, C., Guetta-Weiss, J., Meleveedu, K., Lin, C., Swoboda, D. M., Tremblay, D., & Coltoff, A. (2026). Extended Versus Standard Hypomethylating Agent Dosing in Combination With Venetoclax in Patients With Newly Diagnosed Acute Myeloid Leukemia. Hematological oncology, 44(3), e70198. https://doi.org/10.1002/hon.70198

Disciplines

Medical Education | Medicine and Health Sciences

PubMedID

42142041

Department(s)

USF-LVHN SELECT Program, USF-LVHN SELECT Program Students

Document Type

Article