Menin Inhibitors in Frontline AML Treatment
Recent advancements in the treatment of acute myeloid leukemia (AML) have spotlighted the potential of menin inhibitors, especially when used in frontline settings. Naval G. Daver, MD, from The University of Texas MD Anderson Cancer Center, emphasized the importance of these inhibitors in achieving not just improved median survival but potentially curing patients.
Current Research and Development
The primary focus of ongoing research is to secure regulatory approval for menin inhibitors, a crucial step before these agents can be explored in combination regimens. This includes combinations with minimal residual disease (MRD)-directed therapies or in maintenance settings. Establishing the safety profile, drug-drug interactions, and cardiac effects, such as QTc prolongation, in single-agent trials is essential for their subsequent safe and effective use in combination with other agents.
Leading Menin Inhibitors
Currently, most menin inhibitors are progressing through phase 2 single-arm studies. Revumenib (Revuforj), the first menin inhibitor to enter clinical trials, is leading the development pipeline. Other notable inhibitors include ziftomenib (KO-539), enzomenib (DSP-5336), and bleximenib (JNJ-75276617), each being evaluated in frontline combinations where they are expected to have the most significant effect.
Promising Results from the Beat AML Trial
Preliminary data from a cohort of the phase 1/2 Beat AML trial (NCT03013998) were presented at the 2024 EHA Congress. The trial evaluated the combination of azacitidine (Vidaza), venetoclax (Venclexta), and revumenib in patients with newly diagnosed, treatment-naive AML. As of the data cutoff date of May 1, 2024, patients in the efficacy-evaluable population (n = 24) achieved a composite complete remission rate of 96%, and 92% of patients also attained MRD-negative status. These high response rates suggest potential improvements in MRD clearance and depth of response, which could translate into better overall survival.
Future Directions
Other triplet combinations with ziftomenib, enzomenib, or bleximenib are under investigation, with data expected by late 2025. These findings will provide further clarity on the role of menin inhibitors in improving outcomes for patients with AML, particularly when incorporated into standard or novel therapeutic regimens.
In conclusion, the development of menin inhibitors represents a significant advancement in the treatment of AML, offering hope for improved patient outcomes through innovative combination therapies.
