Midostaurin – the First Targeted Therapy Drug for Patients with Acute Myeloid Leukaemia with FLT3 Mutation

Abstract

The prognosis for patients with acute myeloid leukaemia (AML) varies depending on genetic factors. The presence of mutations in the fms-like tyrosine kinase 3 (FLT3) gene is found in approximately 30% of AML patients. Midostaurin, a first-generation multi-targeted tyrosine kinase inhibitor, is the first FLT3 inhibitor approved for the treatment of newly diagnosed AML patients with the FLT3 mutation in combination with standard induction and consolidation chemotherapy. However, as numerous clinical trials have shown, the list of indications for this drug is likely to be extended. Midostaurin can be administered orally, which improves the patient’s comfort during treatment. In general, it has a favourable safety profile, but interactions with other drugs, such as strong CYP3A4 inhibitors or inducers, which are often used in the concomitant therapy of AML patients, may lead to changes in midostaurin plasma concentrations. In consequence, such interactions may increase the toxicity of the treatment or reduce its therapeutic effect. The aim of this review is to summarise the current knowledge on midostaurin, i.e. its mechanisms of actions, dosage, adverse effects, mechanisms of resistance and limitations to its use. Due to the growing importance of the management of drug-drug interactions mediated via cytochrome CYP3A4, the main focus of this study is the pharmacokinetics of midostaurin and the variability of its plasma concentrations. The Authors emphasise therapeutic drug monitoring with midostaurin as a potential method of managing AML patients with FLT3 mutation.