Comparison of Quizartinib and Midostaurin in FLT3+ AML

A recent development in the field of acute myeloid leukemia (AML) has sparked discussions about the optimal treatment strategies for patients with specific genetic mutations. Dr. Kateryna Fedorov of Vanderbilt University Medical Center sheds light on the factors that should be considered when choosing between quizartinib (Vanflyta) and midostaurin (Rydapt) for patients with FLT3-mutated AML.

Following the FDA approval of quizartinib in 2023 for newly diagnosed, FLT3-ITD–positive AML, the treatment landscape for AML has shifted. Previously, all patients with FLT3-mutated AML receiving induction chemotherapy were treated with midostaurin. While midostaurin is effective in inducing durable complete responses, some patients struggle with gastrointestinal adverse effects and muscle aches associated with this therapy.

On the other hand, quizartinib is a more precise FLT3 inhibitor that specifically targets FLT3-ITD mutations. However, there are still questions about the timing of using this agent for patients with FLT3-ITD–mutated AML. Results from the phase 3 QuANTUM-First trial showed comparable remission rates with quizartinib to those seen with midostaurin in the RATIFY trial, which led to the FDA approval of midostaurin in 2017. However, quizartinib showed a lower median overall survival compared to midostaurin.

Although quizartinib is generally better tolerated than midostaurin, it is important to monitor for QT prolongation. Additionally, while there was hope that older patients with AML may benefit from quizartinib, the data suggest that younger patients see the most benefit. Identifying patients eligible for quizartinib treatment based on their FLT3 ITD mutation status can also pose challenges in gaining timely access to the medication.

In conclusion, the decision between quizartinib and midostaurin for patients with FLT3-mutated AML involves weighing various factors such as efficacy, tolerability, and logistical considerations. Further refinement of the incorporation of quizartinib into real-world clinical practice may be needed in the future.