Quizartinib
Quizartinib, sold under the brand name Vanflyta, is a medication used for the treatment of acute myeloid leukemia. It is a small molecule receptor tyrosine kinase inhibitor. Its molecular target is FLT3, also known as CD135 which is a proto-oncogene. FLT3 mutations are among the most common mutations in acute myeloid leukemia due to internal tandem duplication of FLT3, and the presence of this mutation is a marker of adverse outcome. It was approved for use in Japan in October 2019, and in the United States in July 2023. Medical uses 
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 newly diagnosed acute myeloid leukemia with FLT3 internal tandem duplication (ITD)-positive, as detected by an FDA-approved test. Adverse effects 
The US Food and Drug Administration (FDA) label includes a boxed warning noting QT prolongation, torsades de pointes, and cardiac arrest. Mechanism of action 
Quizartinib selectively inhibits class III receptor tyrosine kinases, including FMS-related tyrosine kinase 3 (FLT3/STK1), colony-stimulating factor 1 receptor (CSF1R/FMS), stem cell factor receptor (SCFR/KIT), and platelet derived growth factor receptors (PDGFRs). Mutations cause constant activation of the FLT3 pathway resulting in inhibition of ligand-independent leukemic cell proliferation and apoptosis. History 
Efficacy of quizartinib with chemotherapy was evaluated in QuANTUM-First (NCT02668653), a randomized, double-blind, placebo-controlled trial of 539 participants with newly diagnosed FLT3 internal tandem duplication positive acute myeloid leukemia. FLT3 internal tandem duplication status was determined prospectively with a clinical trial assay and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay. Participants were randomized (1:1) to receive quizartinib (n=268) or placebo (n=271) with induction and consolidation therapy and as maintenance monotherapy according to the initial assignment. There was no re-randomization at the initiation of post-consolidation therapy. Participants who proceeded to hematopoietic stem cell transplantation initiated maintenance therapy after hematopoietic stem cell transplantation recovery. The main efficacy outcome measure was overall survival, measured from randomization date until death by any cause. The primary analysis was conducted after a minimum follow-up of 24 months after the last patient was randomized. The trial demonstrated a statistically significant improvement in overall survival for the quizartinib arm [hazard ratio (HR) 0.78; 95% CI: 0.62, 0.98; 2‑sided p=0.0324]. The CR rate in the quizartinib arm was 55% (95% CI: 48.7, 60.9) with a median duration of 38.6 months (95% CI: 21.9, NE), and the CR rate in those receiving placebo was 55% (95% CI: 49.2, 61.4) with a median duration of 12.4 months (95% CI: 8.8, 22.7). The FDA granted the application for quizartinib priority review, fast track, and orphan drug designations. Clinical trials
It reported good results in 2012, from a phase II clinical trial for refractory acute myeloid leukemia - in participants who went on to have a stem cell transplant. , it has completed seventeen clinical trials, and another eleven are active. Society and culture

Legal status 
The application for quizartinib was denied in the European Union. References

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4-Morpholinyl compounds
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