Dr Erba on the FDA Approval of Quizartinib Plus Chemotherapy in FLT3-ITD–Positive AML

Harry P. Erba, MD, PhD, professor, medicine, hematologic malignancies, and cellular therapy, member, Duke Cancer Institute, discusses the significance of the FDA approval of quizartinib (Vanflyta) in combination with chemotherapy in patients with newly diagnosed FLT3-ITD–positive acute myeloid leukemia (AML).

On July 20, 2023, the FDA approved quizartinib plus standard cytarabine and anthracycline induction and standard cytarabine consolidation, as well as quizartinib as continuation monotherapy following consolidation, for patients with newly diagnosed AML harboring FLT3-ITD mutations. The approval was supported by findings from the phase 3 QuANTUM-First trial (NCT02668653), in which treatment with quizartinib plus standard chemotherapy and as monotherapy following consolidation led to a median overall (OS) survival of 31.9 months (95% CI, 21.0-not estimable) compared with 15.1 months (95% CI, 13.2-26.2) in patients who received placebo plus chemotherapy (HR, 0.78; 95% CI, 0.62-0.98; P = .032).

FLT3-ITD mutations are more common than TKD mutations in patients with AML and are associated with a higher risk of relapse and a worse overall prognosis, Erba says. The QuANTUM-First study evaluated quizartinib in patients with FLT3-ITD–mutated AML because quizartinib is a second-generation type II FLT3 TKI that only inhibits the FLT3-ITD mutation, Erba explains.

QuANTUM-First was the first randomized clinical trial investigating a FLT3 inhibitor plus intensive chemotherapy that included patients up to 75 years of age who were fit for intensive chemotherapy, Erba emphasizes. In this trial, the median age was 56 years (range, 20-75; interquartile range, 46.0-65.0), and an OS benefit with quizartinib was observed across the entire patient population. This distinguishes QuANTUM-First from the phase 3 RATIFY trial (NCT00651261), which led to the 2017 FDA approval of midostaurin (Rydapt) plus chemotherapy in patients with newly diagnosed FLT3-mutant AML. RATIFY enrolled patients aged 18 to 59 years.

QuANTUM-First provided randomized clinical trial data to support the use of a FLT3-ITD inhibitor in an older patient population fit for intensive chemotherapy, Erba concludes.