Dr Erba on the Safety of Quizartinib By Treatment Phase and Age in FLT3-ITD–positive AML

Harry Erba, MD, PhD, professor, medicine, Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine; director, Leukemia Program, Phase I Development in Hematologic Malignancies, Duke Cancer Institute, discusses the safety profile of quizartinib (Vanflyta) according to treatment phase and age in newly diagnosed patients with FLT3-ITD–positive acute myeloid leukemia (AML), according to the phase 3 QuANTUM-First trial (NCT02668653).

Primary findings from this multicenter, international study demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) in patients who were treated with the quizartinib-based regimen vs those who received chemotherapy plus placebo. Based on these data, the FDA approved quizartinib in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive.

Investigators aimed to describe the safety profile of quizartinib according to treatment phase (induction, consolidation and continuation) and by age group (younger than 60 years vs at least 60 years of age). Results presented at the 2024 EHA Hybrid Congress showed that the safety profile of quizartinib across these treatment phases and age groups supports an overall positive benefit/risk ratio, Erba begins. The toxicities observed in both the quizartinib and placebo groups were similar to those typically seen in patients undergoing intensive chemotherapy, he states. However, there were notable differences that warrant attention, particularly regarding the incidence of neutropenic infections and neutropenia, Erba notes.

Quizartinib was associated with a higher incidence of neutropenic infections and more pronounced neutropenia compared in the placebo group, he reports. This is expected due to quizartinib’s mechanism of action, which involves the inhibition of wild-type FLT3and off-target inhibition of c-KIT at higher doses, leading to increased myelosuppression, Erba explains. Consequently, the risk of infection was higher in the quizartinib group. This correlated with an elevated risk of early mortality at 30 and 60 days, particularly among patients 60 years of age and older, he notes. Although the incidence of 30-day mortality was less than twice as high in the quizartinib group compared with the placebo group, it underscores the need for careful monitoring and management of infections and neutropenia in patients receiving quizartinib, Erba emphasizes.

Another significant toxicity associated with quizartinib is QT prolongation, which has been linked with higher doses of quizartinib in early-phase studies, Erba says. In QuANTUM-First, the rate of grade 3 QTc prolongation was modestly higher in the quizartinib group compared with the placebo group, he details. Notably, there were 2 deaths due to ventricular arrhythmias or sudden death in the quizartinib group, an occurrence not observed in the placebo group, Erba concludes.