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<p>Menin inhibitors (MENINis) represent a novel and promising class of therapeutic agents for acute leukemia (AL). AL subtypes driven by overexpressed <i>HOXA9/MEIS1</i>, such as those characterized by <i>KMT2A</i>-rearranged (<i>KMT2Ar</i>) or <i>NPM1</i>-mutated (<i>NPM1m</i>) AL, display sensitivity to MENINi. Consequently, approximately 40–50% of acute myeloid leukemia (AML) and 5–15% of acute lymphoblastic leukemia (ALL) patients may potentially benefit from MENINi-based therapy. At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Moreover, combination therapies based on MENINis were also reported to be highly effective in refractory/relapsed, or newly diagnosed <i>KMT2Ar</i>- and <i>NPM1m</i>-AML patients. Evidently, MENINis have demonstrated a considerable efficacy in <i>KMT2Ar</i>- and <i>NPM1m</i>-AML patients with a well-tolerance. Furthermore, the therapeutic effects of venetoclax plus azacitidine or "3 + 7" regimens were further enhanced by the addition of MENINis in <i>KMT2Ar</i>- and <i>NPM1m</i>-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes.</p>

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MENIN inhibitor-based therapy in acute leukemia: latest updates from the 2024 ASH annual meeting

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  • 发表日期：

    2025年5月22日

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  • Jiewen Sun,
  • Wenjuan Yu,
  • Xiang Zhang

摘要

Menin inhibitors (MENINis) represent a novel and promising class of therapeutic agents for acute leukemia (AL). AL subtypes driven by overexpressed HOXA9/MEIS1, such as those characterized by KMT2A-rearranged (KMT2Ar) or NPM1-mutated (NPM1m) AL, display sensitivity to MENINi. Consequently, approximately 40–50% of acute myeloid leukemia (AML) and 5–15% of acute lymphoblastic leukemia (ALL) patients may potentially benefit from MENINi-based therapy. At the 2024 ASH annual meeting, updated clinical data regarding monotherapy with MENINis in AL, including revumenib, bleximenib, enzomenib and BN104, were presented. Moreover, combination therapies based on MENINis were also reported to be highly effective in refractory/relapsed, or newly diagnosed KMT2Ar- and NPM1m-AML patients. Evidently, MENINis have demonstrated a considerable efficacy in KMT2Ar- and NPM1m-AML patients with a well-tolerance. Furthermore, the therapeutic effects of venetoclax plus azacitidine or "3 + 7" regimens were further enhanced by the addition of MENINis in KMT2Ar- and NPM1m-AML patients. Therefore, MENINis offer new therapeutic prospects for AML patients, particularly for those with high-risky and poor-prognostic on-target subtypes.