# Clinical Integration of Menin Inhibitors in AML: Evolving Data and Therapeutic Perspectives

## TL;DR

Menin inhibitors are emerging as a promising treatment for certain types of acute myeloid leukemia, with new drugs being developed and tested.

## Contribution

This paper reviews the clinical progress and therapeutic potential of menin inhibitors in AML, including FDA-approved and investigational agents.

## Key findings

- Menin inhibitors target HOX/MEIS1-driven gene expression in AML with KMT2A rearrangements and NPM1 mutations.
- Revumenib and other menin inhibitors show clinical efficacy in relapsed/refractory and frontline AML settings.
- Future research focuses on resistance mechanisms, biomarkers, and combination therapies for improved outcomes.

## Abstract

Acute myeloid leukemia (AML) remains a biologically heterogeneous disease with historically limited targeted therapies and poor outcomes. The development of menin inhibitors represents a promising shift, particularly for patients harboring KMT2A rearrangements (KMT2Ar) and NPM1 mutations (NPM1m). This manuscript reviews the molecular rationale of menin inhibition for aberrant homeobox/myeloid ectopic insertion site 1 (HOX/MEIS1)-driven gene expression and leukemogenesis, clinical trial outcomes, and safety data for menin inhibitors, with a focus on recently FDA-approved revumenib and several other agents in development, ziftomenib (KO-539), bleximenib (JNJ-75276617), and icovamenib (BMF-219). We also focused our discussion on future directions to include resistance mechanisms, biomarker identification and monitoring strategies, and combination therapies. Menin inhibition is now being clinically integrated into relapsed/refractory and frontline treatment settings.