Menin Inhibitors in Acute Myeloid Leukemia—What Does the Future Hold?. Issue 1 (January 2022)

• Record Type: Journal Article
• Authors: Swaminathan, Mahesh; Bourgeois, Wallace; Armstrong, Scott A.; Wang, Eunice S.
• Is Part Of: Cancer journal. Volume 28:Issue 1(2022)
• Page Start: 62
• Page End: 66
• Publication Date: 2022-01
• Subjects: Acute myeloid leukemia -- KMT2A rearrangement -- menin -- NPM1 mutant -- targeted therapy; Cancer -- Periodicals; 616.994005
• DOI: 10.1097/PPO.0000000000000571
• Languages: English
• ISSNs: 1528-9117

Abstract

Abstract: Menin inhibitors constitute a novel class of agents targeting the underlying biology of nucleophosmin ( NPM1 ) mutant and KMT2A (formerly known as MLL1 ) rearranged ( KMT2Ar ) acute leukemias. KMT2Ar acute leukemias constitute 5% to 10% of acute leukemias, and NPM1 mutations are identified in 30% of newly diagnosed acute myeloid leukemias (AMLs). In preclinical AML models, small molecule inhibitors of the menin-KMT2A protein-protein interaction induce differentiation, downregulate critical gene expression programs, and confer a survival advantage in patient-derived xenograft models of NPM1 mutant and KMT2Ar AML. Multiple clinical trials evaluating oral menin inhibitors in acute leukemias are ongoing. Preliminary results in relapsed/refractory NPM1 mutant and KMT2Ar AML have shown on-target effects, tolerable toxicity, and promising clinical activity. This review details the current clinical experience of menin inhibitors in AML and discusses how these agents can be successfully integrated into future therapeutic approaches.