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 approved for the treatment of relapsed or refractory leukemia with rearrangement of KMT2A. In addition, multiple menin inhibitors are currently in clinical development aimed at targeting other additional subsets, such as NPM1 mutations, which form up to 30% of acute myeloid leukemia. However, 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. Significance: Menin inhibitors have the potential to reshape treatment paradigms in acute leukemia. There are multiple promising preclinical combinations that require careful clinical trial design and implementation for a successful translation into the clinical setting.