AMLSG 21-13 phase III results: IC ± dasatinib for CBF-AML

Results from the randomized, open-label, phase III AMLSG 21-13 trial (NCT02013648), comparing intensive chemotherapy (IC) with (n = 100) or without (n = 102) the multi-kinase inhibitor dasatinib in 202 adults with core binding factor (CBF) acute myeloid leukemia (AML), were published in Blood by Döhner et al. The primary endpoint was event-free survival (EFS), while secondary endpoints included overall survival (OS), relapse-free survival (RFS), and cumulative incidence of relapse (CIR). The investigational arm received dasatinib 100 mg once daily (QD) on Days 8–21 of induction and Days 6–28 of consolidation, followed by 12 months of single-agent dasatinib 100 mg QD.

Key data: The addition of dasatinib to standard induction and consolidation chemotherapy followed by 12 months of single-agent dasatinib maintenance therapy did not significantly improve EFS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.63–1.33; p = 0.66), OS (HR, 0.93; 95% CI, 0.53–1.63; p = 0.79), RFS (HR, 0.82; 95% CI, 0.55–1.21; p = 0.31), or CIR (p = 0.37). Four-year EFS rates were 41% in the standard arm vs 44% in the investigational arm. No significant EFS benefit was observed in subgroup analyses according to KIT mutation status, CBF-AML type, age, or sex. Serious adverse events (SAEs) occurred more frequently in the dasatinib arm (64%) than in the standard arm (36%).

Key learning: The addition of dasatinib to intensive chemotherapy failed to improve survival outcomes in patients with CBF-AML and was associated with increased toxicity, questioning the clinical benefit of multi-kinase inhibitors in this patient population.