The ECOG-ACRIN MM20A-EA02 trial, part of the myeloMATCH precision medicine initiative from the US National Institutes of Health, is evaluating a novel combination of venetoclax, hypomethylating agents (HMAs), and gilteritinib for older or unfit patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), according to an abstract presented at the 66th American Society of Hematology Annual Meeting and Exposition.
While there is interest in using FLT3-targeted therapies with lower-intensity treatments, no randomized trials have yet proven they improve survival, the investigators, led by Jessica Altman, MD, of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago, wrote in the abstract.
Previous studies have demonstrated limited survival benefits with venetoclax plus azacitidine, while gilteritinib has shown promise in relapsed or refractory FLT3-mutated AML. Combining these therapies, early-phase studies have reported high complete remission rates and deep molecular responses. However, significant concerns about myelosuppression persist.
This trial randomizes patients into three groups: venetoclax and azacitidine alone, or combined with either continuous or intermittent gilteritinib, and stratified by (<70 years or older) and FLT3-ITD burden (ITD VAF>33% versus lower VAF or D835).
The primary objective is to evaluate the rate of measurable residual disease-negative complete remissions after up to four cycles. Key secondary endpoints include safety data, response rate, event-free survival, and overall survival.
Reference
Altman J, Sun Z, Perl A. A Randomized Phase II Study of Venetoclax and HMA-Based Therapies for the Treatment of Older and Unfit Adults with Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia (AML): A Myelomatch Treatment Trial: ECOG-ACRIN MM20A-EA02. Abstract 2907. Presented at the American Society of Hematology Annual Meeting and Exposition; San Diego, California.
