Midostaurin and emerging FLT3 inhibitors for the treatment of adults with newly diagnosed acute myeloid leukemia with the FLT3 mutation

Abstract

ABSTRACTIntroduction: FLT3 internal tandem duplication mutations are independent risk factors for worse overall survival (OS) and increased relapse risk in AML patients and thus are an attractive target for pharmacotherapy. Midostaurin is the first FLT3 inhibitor approved for the treatment of FLT3-mutant AML. Other tyrosine kinase inhibitors with varying specificity for FLT3 mutations are in development.Areas covered: The authors provide an overview of FLT3 inhibitors, then describe the characterization, clinical efficacy, toxicities, and approval of midostaurin therapy for AML. Discussion was synthesized from primary and review manuscripts addressing FLT3-mutant AML utilizing midostaurin and other FLT3 inhibitors; such were identified by searching the PubMed database for ‘midsotaurin,’ ‘FLT3 inhibitor,’ and ‘FLT3 AML.’ Ongoing clinical trials were identified by searching ClinicalTrials.gov for ‘midostaurin’ and ‘FLT3.’Expert commentary: The addition of midostaurin to standard induction and consolidation chemotherapy in young, fit patients who have newly diagnosed FLT3-mut AML improved OS, event-free survival, and disease-free survival, leading to its international approval. The benefit of adding midostaurin to less intensive therapies in elderly or frail patients is less clear, and has not been evaluated in a randomized trial. The role of midostaurin maintenance therapy after allogeneic hematopoietic cell transplant is an area of active investigation.