Pexidartinib plus FLT3-directed CAR-Macrophage for the treatment of FLT3-ITD-mutated acute myeloid leukemia in preclinical model.

A preprint abstract from biorxiv.org discusses the potential use of pexidartinib, a dual inhibitor of FLT3 and CSF1R, in combination with FLT3-directed chimeric antigen receptor-engineered macrophages (FLT3L-CAR-Macrophage) for the treatment of FLT3-ITD-mutated acute myeloid leukemia (AML). The study found that conditioned medium from FLT3-ITD+ AML cells impaired the phagocytic activities of M2-like leukemia-associated macrophages (M2-LAM) and protected AML cells from FLT3 inhibitor treatment. However, treatment with pexidartinib effectively suppressed M2-LAM, reduced leukemic burden, and prolonged the survival of mice with FLT3-ITD+ AML. Additionally, FLT3L-CAR-Macrophages enhanced phagocytic activities and reduced leukemic burden in vitro and in mice. The study suggests that pexidartinib plus FLT3L-CAR-Macrophage could be a promising therapeutic strategy for FLT3-ITD+ AML, but further investigation is needed. [Extracted from the article]