Improved Survival in FLT3-Mutated Acute Myeloid Leukemia

Patients with acute myeloid leukemia (AML) and FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations have a poor prognosis with standard induction chemotherapy but improved outcomes with the use of a FLT3 inhibitor and allogeneic stem-cell transplantation (alloSCT). Investigators now report the results of a phase 3, industry-sponsored, multinational, double-blind trial in patients with newly diagnosed AML and FLT3-ITD mutations. A total of 539 patients (median age, 56) were randomized to the once-daily oral FLT3 inhibitor quizartinib or placebo, each given in combination with induction and consolidation chemotherapy followed by up to 3 years of maintenance quizartinib or placebo. Patients with a suitable donor also underwent alloSCT consolidation. The primary endpoint was overall survival.

At 39.2 months' follow-up, median overall survival was 31.9 months for the quizartinib group versus 15.1 months for placebo (hazard ratio for death, 0.78; P=0.032). While rates of complete remission were similar in the two groups, the median durations of remission and relapse-free survival were improved with quizartinib. Grade 3 or higher neutropenia was more frequent with quizartinib, and fatal infections occurred in 8% of quizartinib patients versus 4% of placebo patients. Significant QT prolongation, a known side effect of quizartinib, was observed in 2% of patients versus 1% for placebo; two patients in the quizartinib group had cardiac arrest with ventricular fibrillation.