Quizartinib granted FDA approval for patients with newly diagnosed FLT3-ITD mutated AML

On July 20, 2023, quizartinib, an oral, highly potent and selective type II FLT3 inhibitor extensively covered by the AML Hub, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with newly diagnosed (ND) acute myeloid leukemia (AML) with FLT3-internal tandem duplication (FLT3-ITD) mutations.¹

Quizartinib was previously granted priority review by the FDA. The FDA also approved LeukoStrat CDx FLT3 mutation assay as a companion diagnostic for quizartinib.¹ Quizartinib was recently approved in Japan for the treatment of patients with ND FLT3-ITD mutated AML.

FLT3 mutations occur in roughly 37% of ND AML patients; most commonly FLT3-ITD mutations (80%), and are associated with inferior survival outcomes.² This approval is for use in combination with standard cytarabine and anthracycline induction, cytarabine consolidation, and as a maintenance monotherapy. Quizartinib is not currently indicated as maintenance monotherapy post-allogeneic hematopoietic stem cell transplantation.¹

This approval is based on results from the randomized, double-blind, placebo-controlled, phase III QuANTUM-First trial (NCT02668653), which has been previously reported on by the AML Hub. In this trial, quizartinib in combination with cytarabine and anthracycline induction, cytarabine consolidation, and continued as maintenance monotherapy after consolidation, was associated with improved overall survival versus standard chemotherapy alone in patients with ND FLT3-ITD mutated AML (hazard ratio, 0.78; p = 0.0324). Complete remission rates were 55% for both treatment arms; however, quizartinib was associated with a longer median duration of complete remission when compared with standard chemotherapy alone (38.6 months vs 12.4 months, respectively).¹

Quizartinib comes with a Boxed Warning for QT prolongation, torsades de pointes, and cardiac arrest, and is only available through a restricted program under a Risk Evaluation and Mitigation Strategy.¹