Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models

The authors investigate the efficacy of ziftomenib, a selective small molecule inhibitor targeting the menin-KMT2A interaction, in treating acute leukemia characterized by KMT2A rearrangements and NPM1 mutations. They demonstrate that ziftomenib effectively inhibits leukemia cell proliferation and induces differentiation in preclinical models, including those with menin mutations associated with resistance to other inhibitors. The study highlights ziftomenib's potential as a therapeutic option for acute leukemia patients with specific genetic alterations, supported by its recent FDA approval for NPM1-mutated acute myeloid leukemia.