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RESEARCH PRODUCT

Quizartinib in FLT3-ITD-Mutated Relapsed/Refractory Acute Myeloid Leukemia: QuANTUM-R Trial Results

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Abstract Background FLT3-ITD mutations occur in about 25% of patients (pts) with acute myeloid leukemia (AML) and are associated with poor outcomes. Pts with relapsed/refractory (R/R) FLT3-ITD AML have worse prognosis and high unmet medical need. Quizartinib (Q) is a potent and selective FLT3i with promising activity and a manageable safety profile. QuANTUM-R was a global, phase 3, randomized trial of Q vs chemotherapy (SC) in pts with R/R FLT3-ITD AML (NCT02039726). Methods Pts with R/R FLT3-ITD AML w/wo hematopoietic stem cell transplant (HSCT) were randomized to receive Q or a preselected investigator choice SC: low-dose cytarabine; mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and G-CSF with idarubicin (FLAG-IDA). Prior midostaurin was allowed. Pts receiving HSCT after Q could resume Q after HSCT. Primary and secondary endpoints were overall survival (OS) and event-free survival (EFS), respectively. Exploratory endpoints included response rate, time to and duration of response, and transplant rate. Results 367 pts were randomized; 245 to Q and 122 to SC. Median follow-up was 23.5 mo. OS hazard ratio (HR) of Q relative to SC was 0.76 (95% CI, 0.58-0.98; P=.0177). Median OS was 6.2 (95% CI, 5.3-7.2) vs 4.7 (95% CI, 4.0-5.5) mo in Q and SC arms, respectively. EFS HR was 0.90 (95% CI, 0.70-1.16; P=.1071); median EFS was 1.4 (95% CI, 0.0-1.9) vs 0.9 (95% CI, 0.4-1.3) mo, respectively. Sensitivity analyses and OS subgroup analyses supported Q vs SC. Composite complete response (CRc) was 48% and 27% in Q and SC arms, respectively. Transplant rate was 32% (Q) and 12% (SC). Median time to first CRc was 4.9 wk for Q. The most common grade ≥ 3 TEAEs in both arms were infections and those associated with cytopenia. Conclusion OS benefit was observed with single-agent Q vs SC in pts with R/R FLT3-ITD AML with a favorable Q safety profile, providing evidence of meaningful clinical benefit in pts with limited treatment options.