quizartinib — Drug Monograph

Brand names: Vanflyta

Drug class: FLT3 Inhibitor

Mechanism of Action

Quizartinib is a highly selective, potent second-generation inhibitor of FLT3-ITD (internal tandem duplication), with markedly greater selectivity for FLT3 compared to first-generation inhibitors. It binds to the inactive (DFG-out) conformation of the FLT3 kinase domain, blocking constitutive FLT3 auto-phosphorylation and downstream activation of STAT5, RAS/MAPK, and PI3K/AKT signaling. Its selectivity profile reduces off-target kinase inhibition and is associated with deeper, more durable FLT3 suppression during maintenance therapy.

FDA Indications

• Newly diagnosed FLT3-ITD-positive AML in adults, in combination with standard induction and consolidation chemotherapy, followed by single-agent maintenance — approved Jul 2023 (QuANTUM-First trial)

Common Side Effects

• Nausea
• Febrile neutropenia
• Mucositis / stomatitis
• Diarrhea
• Fatigue
• QTc prolongation
• Constipation
• Edema
• Elevated transaminases
• Headache
• Thrombocytopenia
• Anemia

Clinical Pearl

Quizartinib is the only FLT3 inhibitor approved for use in the frontline setting that includes a maintenance phase after allogeneic stem cell transplant, making it critical to distinguish its role from midostaurin (which has no approved maintenance indication). In the QuANTUM-First trial, the overall survival benefit was most pronounced in the maintenance phase, highlighting that durable FLT3 suppression post-transplant drives the clinical benefit. Because quizartinib lacks meaningful activity…

Related Therapies & Mechanisms

• Gilteritinib (Xospata) — FLT3 Inhibitor · Leukemia
• Midostaurin (Rydapt) — FLT3 Inhibitor · Leukemia
• Acalabrutinib (Calquence) — Leukemia
• Alemtuzumab (Campath) — Leukemia