Quizartinib for the treatment of acute myeloid leukemia

Introduction . Up to 30% of patients with acute myeloid leukemia (AML) have a mutation in the FLT3 receptor. Molecular targets have acquired a significant interest in the treatment of AML and are changing patient outcomes, including improvement of overall survival (OS) and remission rates. FLT3 inhibitors have obtained a central role in how we treat AML. Areas covered . This article reviews the mechanism of action, pharmacology, clinical efficacy, and safety of quizartinib, a FLT3 inhibitor, for the treatment of acute myeloid leukemia. Expert opinion . Quizartinib yielded an improvement in OS and complete remission (CR) rates in a phase 3 trial for relapsed/refractory FLT3-mutated AML. The toxicities are manageable; however, it is associated with significant QTc prolongation and myelosuppression. The FDA and EMA did not grant drug approval to quizartinib in the relapsed/refractory setting due to the lack of a significant benefit - to-risk ratio, safety concerns and concerns with credibility and generalizability of the trial data. Results from the frontline phase 3 study evaluating quizartinib with intensive chemotherapy are eagerly awaited. Ongoing studies are investigating its toxicity and efficacy with other therapeutic agents and will help to clarify its role in the treatment ofFLT3-ITD-mutated AML.