On July 20, 2023, quizartinib was approved for use with standard cytarabine and anthracycline induction and cytarabine consolidation and as maintenance monotherapy following consolidation chemotherapy in adults with newly diagnosed acute myeloid leukemia that is FLT3 internal tandem duplication (ITD)-positive, as detected by a U.S. Food and Drug Administration (FDA)-approved test.1
Quizartinib is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation; improvement in overall survival with the agent in this setting has not been demonstrated.
The FDA also approved LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic for quizartinib.
Supporting Efficacy Data
Approval was supported by the double-blind QuANTUM-First trial (ClinicalTrials.gov identifier NCT02668653), in which 539 patients were randomly assigned to receive quizartinib (n = 268) or placebo (n = 271) with induction and consolidation therapy and as maintenance monotherapy. The primary analysis of overall survival was performed at a minimum follow-up of 24 months after the random assignment of the last patient. Overall survival was significantly improved in the quizartinib group (hazard ratio = 0.78, 95% confidence interval = 0.62–0.98, P = .0324). The complete response rate was 55% vs 55%, and the median duration of response was 38.6 vs 12.4 months.
How It Is Used
Treatment is in 28-day cycles. For induction, the recommended dose of quizartinib is 35.4 mg once daily on days 8 to 21 of “7 + 3” chemotherapy (cytarabine on days 1–7 plus daunorubicin or idarubicin on days 1–3) and on days 8 to 21 or 6 to 19 of an optional second induction (“7 + 3” or “5 + 2” [5 days of cytarabine plus 2 days of daunorubicin or idarubicin]). For consolidation, 35.4 mg of quizartinib is given once daily on days 6 to 19 with high‑dose cytarabine on days 1, 3, and 5 for up to four cycles. For maintenance, 26.5 mg of quizartinib is given once daily on days 1 to 14, and 53 mg is given once daily on days 15 through 28 thereafter for up to 36 28-day cycles.
In QuANTUM-First, the most common adverse events of any grade in the quizartinib/chemotherapy group with an incidence of at least 2% higher vs the placebo/chemotherapy group were febrile neutropenia (44% vs 42%), diarrhea (42% vs 39%), mucositis (38% vs 33%), nausea (34% vs 31%), abdominal pain (30% vs 22%), and sepsis (30% vs 26%). The most common grade 3 or 4 adverse events in the quizartinib group included febrile neutropenia (43% vs 41%), neutropenia (26% vs 12%), and sepsis (19% vs 20%).
The most common serious adverse event in the quizartinib group was febrile neutropenia (11%). Adverse events, mainly sepsis (5%), led to discontinuation of treatment in 20% of patients. Fatal adverse events, mainly sepsis (5%), occurred in 10% of patients.
Quizartinib has boxed warnings for QT prolongation, torsades de pointes, and cardiac arrest. Quizartinib is available only through a Risk Evaluation and Mitigation Strategy (REMS) program called Vanflyta REMS.
Quizartinib also has warnings/precautions for QT prolongation, torsades de pointes, and cardiac arrest; and embryofetal toxicity. It is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, and in those with a history of ventricular arrhythmia or torsades de pointes.
1. Vanflyta (quizartinib) tablets, for oral use, prescribing information, Daiichi Sankyo, Inc, July 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216993s000lbl.pdf. Accessed August 1, 2023.