Dr Montesinos on Quizartinib Plus Chemotherapy in Newly Diagnosed FLT3-ITD Wild-Type AML

Pau Montesinos, MD, PhD, attending physician, hematologist, University Hospital La Fe, Valencia, Spain, discusses preliminary efficacy seen with the addition of quizartinib to standard 7+3 chemotherapy in patients with newly diagnosed FLT3-ITD wild-type acute myeloid leukemia (AML).

The phase 2 QUIWI trial (NCT04107727) was designed to compare event-free survival (EFS) outcomes with the combination vs placebo. The trial was composed of a safety run-in portion followed by a double-blind randomization phase. Patients with newly diagnosed FLT3-ITD wild-type AML who were fit for intensive chemotherapy were enrolled on the trial and stratified according to age. Notably, these patients were centrally screened for FLT3-ITD before being randomized 2:1 to the experimental vs control regimen.

Early efficacy data from the first interim analysis of this trial were reported at the 2023 EHA Congress. At a median follow-up 21 months, the quizartinib combination produced a median EFS of 16.5 months vs 10.6 months with placebo (HR, 0.741; 95% CI, 0.535-1.026; 2-sided P= .059), Montesinos reports. This indicates a trend towards improved EFS with the combination, he says. Significant improvement in relapse-free survival (RFS) was also observed, Montesinos adds. Median RFS was 18.6 months with placebo and was not reached with quizartinib plus chemotherapy.

Moreover, the 3-year overall survival (OS) rate was approximately 40% in the placebo arm and 60% in the experimental arm, Montesinos continues. Median OS was 20.2 months with placebo and was not reached with the combination (HR, 0.569; 95% CI, 0.385-0.841; 2-sided P= .004).

The composite complete response (cCR) rates were comparable in both arms, Montesinos states. After 1 or 2 induction cycles, the cCR rate was 78% in both study arms, while the CR/CR with incomplete hematologic recovery rate with minimal residual disease (MRD) negativity was 44% vs 43% with the combination and placebo, respectively. Although the regimen did not improve cCR rates vs placebo, significant increases in both EFS and RFS indicate its potential long-term benefit in this population, Montesinos concludes.