Addition of Quizartinib to Chemotherapy in Newly Diagnosed FLT3-ITD–Positive Acute Myeloid Leukemia

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As reported in The Lancet by Erba et al, the phase III QuANTUM-First trial has shown prolonged overall survival with the addition of the FLT3 inhibitor quizartinib to chemotherapy in patients with newly diagnosed FLT3-internal-tandem-duplication (ITD)-positive acute myeloid leukemia (AML).

Study Details


  • Quizartinib plus chemotherapy prolonged overall survival vs placebo plus chemotherapy.
  • Median overall survival was 31.9 months vs 15.1 months.

In the double-blind trial, 539 patients aged 18–75 years from sites in 26 countries were randomly assigned between September 2016 and August 2019 to receive quizartinib (n = 268) or placebo (n = 271) plus chemotherapy. Induction therapy consisted of cytarabine at 100 mg/m² per day via continuous infusion from day 1 to 7 and anthracycline (daunorubicin at 60 mg/m² per day or idarubicin at 12 mg/m² per day) on days 1, 2, and 3, then quizartinib at 40 mg or placebo once per day starting on day 8 for 14 days. Patients with complete remission or complete remission with incomplete neutrophil or platelet recovery received consolidation with high-dose cytarabine plus quizartinib at 40 mg per day or placebo, allogeneic hematopoietic cell transplantation (allo-HCT), or both, followed by continuation of single-agent quizartinib or placebo for up to 3 years. The primary endpoint was overall survival in the intent-to-treat population.  

Overall Survival

Median follow-up was 39.2 months (interquartile range = 31.9–45.8 months). A total of 173 patients in the quizartinib group and 175 in the control group proceeded to consolidation and 116 and 92 entered continuation. Median overall survival was 31.9 months (95% confidence interval [CI] = 21.0 months to not estimable) in the quizartinib group vs 15.1 months (95% CI = 13.2–26.2 months) in the control group (hazard ratio [HR] = 0.78, 95% CI = 0.62–0.98, P = .032). HRs favored quizartinib across most prespecified subgroups. In a post hoc subgroup analysis by age, the HRs were 0.68 (95% CI = 0.49–0.95) among patients aged < 60 years and 0.91 (95% CI = 0.66–1.26) among those aged ≥ 60 years. Event-free survival was not significantly prolonged in the quizartinib group (HR = 0.92 (95% CI = 0.75–1.11, P = .24).

Among 147 patients in the quizartinib group and 150 in the control group with complete remission during induction, median relapse-free survival was 39.3 months (95% CI = 22.6 months to not estimable) in the quizartinib group vs 13.6 months (95% CI = 9.7–23.7 months) in the control group (HR = 0.61, 95% CI = 0.44–0.85). Among these patients, the cumulative incidence of relapse at 12, 24, and 36 months was 19% vs 35%, 31% vs 43%, and 34% vs 45%.

Adverse Events

Grade ≥ 3 adverse events occurred in 92% of the quizartinib group and 90% of the control group. The most common grade 3 or 4 adverse events were febrile neutropenia (43% vs 41%), hypokalemia (19% vs 16%), and pneumonia (11% vs 11%) in both groups and neutropenia (18% vs 9%) in the quizartinib group. Serious adverse events occurred in 56% vs 44% of patients, most commonly febrile neutropenia (11% vs 8%). Adverse events led to treatment discontinuation in 20% vs 9% of patients. Adverse events led to death in 11% vs 10% of patients, most commonly infection (8% vs 4%).

The investigators concluded: “The addition of quizartinib to standard chemotherapy with or without allo-HCT, followed by continuation monotherapy for up to 3 years, resulted in improved overall survival in adults aged 18–75 years with FLT3-ITD–positive newly diagnosed AML. 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.”

Harry P. Erba, MD, Duke Cancer Institute, is the corresponding author for The Lancet article.

Disclosure: The study was funded by Daiichi Sankyo. For full disclosures of the study authors, visit

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