Role of FMS-Like Tyrosine Kinase 3 (FLT3) Inhibitors in a Patient With T/Myeloid Acute Leukemia With an FLT3 Mutation.

Mixed-phenotype acute leukemia (MPAL) is a rare and aggressive hematologic malignancy characterized by the co-expression of myeloid and lymphoid markers, posing diagnostic and therapeutic challenges. The presence of FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation, common in acute myeloid leukemia (AML) but rare in MPAL, introduces further uncertainty regarding optimal treatment strategies, particularly regarding the use and timing of FLT3 inhibitors. We report a case of a 59-year-old man who presented with marked leukocytosis and systemic symptoms. Diagnostic workup, including flow cytometry and bone marrow biopsy, confirmed MPAL, T-cell/myeloid type, with an FLT3-ITD mutation. The patient was initially treated with a hybrid induction regimen of FLAG-IDA (fludarabine, arabinofuranosyl cytidine, granulocyte colony-stimulating factor (G-CSF)-idarubicin) plus vincristine and prednisone, followed by reinduction with decitabine and venetoclax due to persistent disease. Morphologic and immunophenotypic remission was achieved, and the patient was bridged to allogeneic stem cell transplantation. Midostaurin, an FLT3 inhibitor, was introduced in the post-remission and pre-transplant consolidation phases to reduce toxicity. This case highlights the diagnostic complexity and therapeutic uncertainty associated with FLT3-mutated MPAL. While FLT3 inhibitors are standard in AML, their role in MPAL remains undefined, with few case reports being published on this topic. Our case highlights the importance of individualized treatment planning and supports further research into the optimal timing and integration of targeted therapy in MPAL. FLT3-ITD mutation in MPAL presents a unique therapeutic dilemma. In this case, the delayed introduction of midostaurin was favored to minimize toxicity during induction. Ongoing studies are needed to determine the best treatment strategies and timing for targeted therapies in this rare leukemia subtype.