Quizartinib Approved for Newly Diagnosed Acute Myeloid Leukemia

Acute myeloid leukemia

The FDA has approved quizartinib (Vanflyta®, Daiichi Sankyo, Inc.) for treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive, as detected by the FDA’s newly approved companion diagnostic for quizartinib, LeukoStrat CDx FLT3 Mutation Assay. Quizartinib is added to standard cytarabine and anthracycline induction therapy, cytarabine consolidation therapy, and maintenance quizartinib monotherapy following consolidation chemotherapy.  

Why it matters: “Patients with AML positive for ITD mutations of FLT3 have poor outcomes,” wrote Harry P. Erba, MD, Professor of Medicine at Duke Cancer Institute, and colleagues, in their published results of the QuANTUM-First Trial (NCT02668653), on which approval was based. “Quizartinib, an oral, highly potent, selective, type 2 FLT3 inhibitor, plus chemotherapy showed antitumor activity with an acceptable safety profile in patients with FLT3-ITD–positive newly diagnosed AML.”

What they studied: The safety and efficacy of quizartinib were studied in the phase 3, double-blind, placebo-controlled trial in which 539 patients with newly diagnosed FLT3-ITD–­positive AML were randomized 1:1 to receive either quizartinib or placebo. Each arm received induction therapy, consisting of up to two cycles of cytarabine and daunorubicin or idarubicin, followed by quizartinib 40 mg or placebo once daily; and consolidation therapy, consisting of up to four cycles of cytarabine, followed by quizartinib or placebo and/or hematopoieitic stem cell transplant (HSCT). The continuation period lasted for up to 36 cycles after consolidation therapy. For those who proceeded to HSCT, maintenance therapy was conducted following HSCT recovery. The primary end point measured was overall survival.

What they found: At a minimum follow-up of 24 months following the last patient’s randomization, overall survival saw a significant improvement in the quizartinib arm compared with placebo (hazard ratio 0.78). Complete response was 55% in the quizartinib arm, with a median duration of 38.6 months, compared with a complete response of 55% and median duration of 12.4 months in the placebo arm.

Adverse events: Please see prescribing information for the full list of potential adverse events.

What to know:

  • Maintenance monotherapy with quizartinib following allogeneic HSCT is not indicated because improvement in overall survival has not been demonstrated in this setting
  • The prescribing info for quizartinib includes a boxed warning for QT prolongation, Torsades de Pointes, and cardiac arrest
  • Treatment with quizartinib is currently only available through the restricted program known as the Vanflyta® Risk Evaluation and Mitigation Strategy (REMS)

Conclusion: “Based on the results from the QuANTUM-First trial, quizartinib provides a new, effective, and generally well-tolerated treatment option for adult patients with FLT3-ITD–positive newly diagnosed AML,” concluded Dr. Erba and colleagues.

Instructions: The dosage of quizartinib recommended for induction therapy, followed by consolidation therapy, and ending with maintenance therapy, is as follows:

Induction therapy: Quizartinib 35.4 mg orally once daily on Days 8-21 of “7 + 3” induction (cytarabine 100 or 200 mg/m2/day on Days 1-7 plus daunorubicin 60 mg/m2/day or idarubicin 12 mg/m2/day on Days 1-3) and on Days 8-21 or 6-19 of an optional second induction cycle (“7 + 3” or “5 + 2” [5 days cytarabine plus 2 days daunorubicin or idarubicin], respectively)

Consolidation therapy: Quizartinib 35.4 mg orally once daily on Days 6-19 of high‑dose cytarabine (1.5-3.0 g/m2 every 12 hours on Days 1, 3, and 5) for up to 4 cycles

Maintenance therapy: Quizartinib 26.5 mg orally once daily on Days 1-14 and 53 mg once daily, thereafter, for up to 36 cycles of 28 days

For More Information

Erba HP, Montesinos P, Kim HJ, et al (2023). Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet, 401(10388):1571-1583. DOI:10.1016/S0140-6736(23)00464-6

Clinicaltrials.gov (2023). Quizartinib with standard of care chemotherapy and as continuation therapy in patients with newly diagnosed FLT3-ITD (+) acute myeloid leukemia (AML) (QuANTUM-First). NLM identifier: NCT02668653.

Vanflyta® (quizartinib) prescribing information (2023). Daiichi Sankyo, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216993s000lbl.pdf

US Food and Drug Administration (2023). FDA approves quizartinib for newly diagnosed acute myeloid leukemia. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-quizartinib-newly-diagnosed-acute-myeloid-leukemia

Image credit: National Institutes of Health. Licensed under: Public Domain

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