Quizartinib significantly improved overall survival in patients with acute myeloid leukaemia (AML) with an FLT3 internal tandem duplication (FLT3/ITD) mutation, regardless of whether they achieve a remission with allogeneic hematopoietic cell transplantation (aHCT) and also despite minimal residual disease (MRD) status prior to aHCT.
It provides a clinically meaningful and statistically significant improvement in overall survival compared with standard induction and consolidation therapy alone.
The phase 3 QuANTUM-First trial was the first randomized trial to focus on patients with FLT3-ITD mutations, who face uniquely poor outcomes.
The study involved 539 patients with newly diagnosed AML who had FLT3-ITD positivity.
Those who achieved either a complete remission or complete remission with incomplete hematologic recovery received up to 4 cycles of high-dose cytarabine plus quizartinib 40 mg/day or placebo and/or aHCT, followed by up to 3 years of quizartinib continuation treatment (30-60 mg/day) or placebo.
While the rates of complete remission between the quizartinib and placebo group were similar (54.9% and 55.4%), the rate of incomplete remission after induction was higher in the quizartinib group (16.8% vs 9.6%).
Of those achieving a first complete remission, 57.1% on quizartinib and 48.7% on placebo went on to receive aHCT, at a median time of 3.5 months in the quizartinib group and 3.3 months in the placebo group.
Subsequently, 72.6% and 49.3% started 3 years of continued treatment.
The results showed that quizartinib treatment was favorably associated with overall survival, with a 23% risk reduction of death as was aHCT in first complete response, with a 58% risk reduction after a multivariate adjustment for factors including region, age, and white blood count, including aHCT in first complete remission.
In a first complete remission and overall survival indicated that patients on quizartinib who had a complete response had longer overall survival regardless of having undergone aHCT in first complete response or not.
Those receiving aHCT in a complete remission had longer overall survival in the quizartinib group based on MRD status compared with placebo, particularly among patients with pre-aHCT MRD positivity.