On July 20, 2023, the FDA approved quizartinib (Vanflyta; Daiichi Sankyo) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy after consolidation chemotherapy, for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3-internal tandem duplication (ITD)–positive, as detected by an FDA-approved test.
Quizartinib is an orally administered small-molecule inhibitor of the tyrosine kinase receptor FLT3.
The efficacy of quizartinib plus chemotherapy was evaluated in QuANTUM-First, a randomized, double-blind, placebo-controlled clinical trial of 539 patients with newly diagnosed FLT3-ITD–positive AML. FLT3-ITD status was determined prospectively with a clinical trial assay and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.
Patients were randomized to receive quizartinib (n=268) or placebo (n=271) with induction and consolidation therapy and as maintenance monotherapy according to the initial assignment. Efficacy was established on the basis of overall survival (OS), which was measured from the date of randomization until death by any cause. The primary analysis was conducted after a follow-up of ≥24 months after the randomization of the last patient. Results showed a significant improvement in OS in the quizartinib arm (hazard ratio, 0.78; 95% confidence interval, 0.62-0.98; 2-sided P=.0324).
Quizartinib is not indicated as maintenance monotherapy in patients who have received allogeneic hematopoietic stem cell transplantation; improvement in OS with quizartinib in this setting has not been demonstrated.
Quizartinib is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) program called Vanflyta REMS because of the serious risk for QT prolongation, torsades de pointes, and cardiac arrest. A boxed warning is included in the prescribing information for quizartinib.
The requirements of the Vanflyta REMS program include:
A treatment course of quizartinib consists of ≤2 cycles of quizartinib in combination with induction cytarabine and anthracycline, ≤4 cycles of quizartinib in combination with high-dose cytarabine consolidation, and ≤36 cycles of quizartinib as maintenance therapy or until disease progression or unacceptable adverse reactions. Quizartinib maintenance therapy should be initiated after consolidation chemotherapy once the absolute neutrophil count is >500/mm3 and the platelet count is >50,000/mm3.
