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 ...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.展开更多
文摘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.
