Sinapsos Podcast | Oncology

E29 - Menin Inhibition New Target for Leukemia

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E29   |  12 min   |   Latest   |  Publication Link

  • Podcast based on: Alati, C.; Molica, M.; Pitea, M.; Marafioti, V.; Porto, G.; Policastro, G.; Bilardi, E.; Utano, G.; Giordano, L.; Sgarlata, A.; Delfino, I.M.; Idato, A.; Santoro, G.; Rossi, M.; Martino, M. Menin Inhibition in Acute Myeloid MLL Rearranged Leukemias: A New Target for Precision Care. Cancers 2026, 18, 637. https://doi.org/10.3390/cancers18040637
    • Type: Review  |  Publication date: 15 February 2026

  • Summary: Menin inhibitors are new targeted drugs for two high-risk types of acute leukemia (KMT2A-rearranged and NPM1-mutated). Revumenib was approved in 2024–2025. In heavily pretreated patients, about 23% achieved complete remission, with most of those becoming MRD-negative. Ziftomenib, bleximenib, and enzomenib show similar effectiveness but differ in side effects, particularly heart rhythm problems (QTc prolongation varies among drugs). When combined with other drugs like azacitidine/venetoclax or chemotherapy, response rates are much higher in newly diagnosed patients, suggesting these could work as initial treatment. About 40% of patients develop resistance, usually through MEN1 gene mutations. Different menin inhibitors have different resistance patterns, so switching drugs might help. About 30–40% of responders went on to stem cell transplant, which remains the best chance for cure. Menin inhibitors are the first targeted therapies for these aggressive leukemias, showing promise both alone and in combinations, though resistance remains a challenge.

  • Keywords: menin inhibitors; KMT2A rearrangements; MLL rearrangements; NPM1 mutations; acute myeloid leukemia; revumenib; precision medicine; targeted therapy

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