Midostaurin for FLT3-mutated Acute Myeloid Leukaemia – Considerations for optimal use

Midostaurin is the first oral fms-related tyrosine kinase 3 (FLT3) inhibitor to significantly extend survival for patients with FLT3 mutated acute myeloid leukaemia (AML) in combination with standard chemotherapy. However, the optimum use of midostaurin in AML remains an active area of research, and a number of practical aspects require consideration when prescribing the agent. Midostaurin and its metabolites are both inhibitors and inducers for CYP3A, raising the potential for drug–drug interactions with CYP3A4 modulators/CYP3A substrates such as antifungal agents. Also, while midostaurin has generally demonstrated good tolerability in clinical trials, including in high-risk patients and in the elderly, its use is associated with certain adverse events such as gastrointestinal toxicity and rash, which may require management (for example through the use of prophylactic antiemetics) and could be treatment-limiting in a minority of patients. However, overall, midostaurin represents an effective treatment for use in combination therapy in newly diagnosed patients with AML and an FLT3 mutation, and may be particularly useful for those unable to tolerate intensive induction therapy, such as the elderly.