QuANTUM-First: A post hoc analysis of the impact of allo-HSCT and quizartinib in newly diagnosed FLT3-ITD-positive AML

Quizartinib, a selective FLT3 inhibitor, has been approved by the US Food and Drug Administration for newly diagnosed FLT3-ITD AML in combination with chemotherapy, based on the data from the QuANTUM-First trial (NCT02668653). A post hoc analysis from the QuANTUM-First phase III trial assessing the impact of allo-HSCT and quizartinib in patients with FLT3-ITD AML in CR1 and CRc1 was published by Schlenk et al. in Haematologica.

A total of 144 and 128 patients in the quizartinib and placebo groups, respectively, from the ITT population (N = 539) underwent allo-HSCT. Outcomes included OS in CR1 and CRc1, RFS, and safety.

Key learnings

In patients who achieved CR1 by the end of induction, quizartinib and allo-HSCT were predictors of longer OS (HR, 0.553; p = 0.0015 and HR, 0.527; p = 0.0023, respectively).

Quizartinib (HR, 0.645; p = 0.0068) and allo-HSCT (HR, 0.557; p = 0.0012) provided an OS advantage for patients who achieved CRc1 by the end of induction. RFS was longer among patients achieving CR/CRc, irrespective of undergoing allo-HSCT or not (HR, 0.607 and HR, 0.682, respectively).

Among patients undergoing allo-HSCT, aGvHD occurred in 45.1% vs 38.5% and cGvHD in 29.4% vs 19.8% of patients in the quizartinib and placebo groups, respectively. Grade 3–4 aGvHD rates were higher in the quizartinib group compared with placebo (16.7% vs 6.6%). No new safety signals were identified.

Data from this QuANTUM-First post hoc analysis supports quizartinib and allo-HSCT as an effective and well-tolerated treatment strategy for newly diagnosed FLT3-ITD AML. The small sample size and variation in allo-HSCT eligibility based on the investigator’s decision should be considered when interpreting the results.