Combination Strategies with Menin Inhibitors for Acute Leukemia

Abstract Menin inhibitors are targeted therapies for the treatment of genetically defined subsets of acute leukemia. The menin inhibitor revumenib is currently approved for relapsed or refractory leukemia with rearrangement of lysine methyltransferase 2 A (KMT2A). However, multiple other menin inhibitors are currently in clinical development aimed at targeting additional subsets such as nucleophosmin 1 (NPM1) mutations which form up to 30% of acute myeloid leukemia. As observed with other targeted therapies for cancer, on-target resistance mutations emerged in advanced cases following monotherapy. Therefore, combination strategies incorporating menin inhibitors are needed to improve durability and depth of remission.