Midostaurin abrogates CD33-directed UniCAR and CD33-CD3 bispecific antibody therapy in acute myeloid leukemia

Combinatory therapeutic approaches of different targeted therapies in acute myeloid leukemia (AML) are currently under preclinical and early clinical investigation. To enhance anti-tumor effects, we combined tyrosine kinase inhibitor (TKI) Midostaurin and T cell-mediated immunotherapy directed against CD33. We show that clinically relevant concentrations of Midostaurin abrogate T cell-mediated cytotoxicity both after activation with bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells. This information is of relevance for clinicians exploring T cell-mediated immunotherapy in early clinical trials. Given the profound inhibition of T cell functionality and anti-tumor activity, we recommend favoring specific fms-like tyrosine kinase 3 (FLT3) TKIs for further clinical testing of combinatory approaches with T cell-based immunotherapy.