FDA Approves Quizartinib for Newly Diagnosed FLT3-ITD–Positive Acute Myeloid Leukemia

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On July 20, the U.S. Food and Drug Administration (FDA) approved quizartinib (Vanflyta) with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive, as detected by an FDA-approved test. The FDA also approved the LeukoStrat CDx FLT3 Mutation Assay as a companion diagnostic for quizartinib.

QuANTUM-First Trial

Efficacy of quizartinib with chemotherapy was evaluated in QuANTUM-First ( identifier NCT02668653), a randomized, double-blind, placebo-controlled trial of 539 patients with newly diagnosed FLT3-ITD–positive AML. FLT3-ITD status was determined prospectively with a clinical trial assay and verified retrospectively with the companion diagnostic LeukoStrat CDx FLT3 Mutation Assay.

Patients were randomly assigned 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–random assignment at the initiation of postconsolidation therapy. Patients who proceeded to hematopoietic stem cell transplantation (HSCT) initiated maintenance therapy after HSCT recovery.

The main efficacy outcome measure was overall survival, measured from random assignment date until death by any cause. The primary analysis was conducted after a minimum follow-up of 24 months after the last patient was randomly assigned.

Overall Survival Results

The trial demonstrated a statistically significant improvement in overall survival for the quizartinib arm [hazard ratio (HR) = 0.78, 95% confidence interval [CI] = 0.62–0.98; two‑sided P = .0324]. The complete response 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 months to not evaluable); complete response rate in those receiving placebo was 55% (95% CI = 49.2%–61.4%), with a median duration of response of 12.4 months (95% CI = 8.8–22.7 months).

Quizartinib is not indicated as maintenance monotherapy following allogeneic HSCT. Improvement in overall survival with quizartinib has not been demonstrated in this setting.

A boxed warning for quizartinib notes QT prolongation, torsades de pointes, and cardiac arrest. Quizartinib is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Vanflyta REMS. See the prescribing information for a full list of reported adverse reactions.

The recommended quizartinib doses follow:

  • Induction: 35.4 mg orally once daily on days 8 to 21 of “7 + 3” (cytarabine [100 or 200 mg/m2/d] on days 1–7 plus daunorubicin [60 mg/m2/d] or idarubicin [12 mg/m2/day] on days 1–3) and on days 8–21 or 6–19 of an optional second induction (“7 + 3” or “5 + 2” [5 days cytarabine plus 2 days daunorubicin or idarubicin], respectively)
  • Consolidation: 35.4 mg orally once daily on days 6 to 19 of high‑dose cytarabine (1.5 to 3 g/m2 every 12 hours on days 1, 3, and 5) for up to four cycles
  • Maintenance: 26.5 mg orally once daily on days 1 to 14 and 53 mg once daily thereafter for up to 36 28-day cycles.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Fast Track designation, and Orphan Drug designation.


The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.