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

  • Oncol Res. 2026 Feb 24;34(3):4. doi: 10.32604/or.2025.072443.
Tiffany Chen  1 ,  Grace Kim  2 ,  Yekta Rahimi  3 ,  Monisha Kamdar  4 ,  Eduardo Fernandez-Hernandez  4 ,  Karrune Woan  4 ,  Eric L Tam  4 ,  George Yaghmour  4
Affiliations
  • 1. California University of Science and Medicine, Colton, CA 92324, USA.
  • 2. Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA.
  • 3. Department of Medicine, Keck School of Medicine of USC, Los Angeles, CA 90033, USA.
  • 4. Jane Ann Nohl Division of Hematology and Center for the Study of Blood Disease, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
PMID: 41799513 DOI: 10.32604/or.2025.072443
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.

Keywords
Menin; acute myeloid leukemia (AML); bleximenib; icovamenib; leukemia; menin inhibitor; revumenib; ziftomenib.
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