Quizartinib

Quizartinib is an oral and potent fms-like tyrosine kinase 3 (FLT3) inhibitor and it is the first drug developed specifically targeting FLT3, as other agents with FLT3 inhibition activities were investigated with other targets in mind. Additionally, quizartinib also demonstrates inhibitory activity toward FLT3 with internal tandem duplication (ITD), although with a 10-fold lower affinity compared to wild-type FLT3. FLT3-ITD mutation is present in 75% of FLT3-mutated AML, leading to constitutively active FLT3 and thus poorer overall survival and higher risk of relapse. Multiple clinical trials have demonstrated quizartinib's efficacy in relapsed/refractory FLT3-ITD mutant AML. Therefore, quizartinib is proven to be a beneficial addition to the current AML treatment regimen, although serious side effects such as QT prolongation necessitates further research to optimize quizartinib's addition to AML standard of care.

Quizartinib was approved by the FDA in July 2023 and developed under the brand name VANFLYTA by Daiichi Sankyo. The FDA approval was based on positive results from the QuANTUM-First trial for FLT3-ITD positive AML, where quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation, followed by a maintenance monotherapy resulted in a 22% reduction in the risk of death.

Quizartinib is indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test.