AIEOP-BFM ALL 2009 phase III trial results: Reducing daunorubicin in children with B-ALL

Results from the randomized phase III AIEOP-BFM ALL 2009 trial (NCT03643276), assessing the need for anthracyclines in children with non-high-risk B-cell acute lymphoblastic leukemia (B-ALL), were recently published in the Journal of Clinical Oncology by Gottschalk et al. Following two doses of daunorubicin (DNR) during induction therapy, patients were randomly assigned to receive two additional DNR doses in the control arm (CA) (n = 1,040) while the experimental arm (EA) (n = 1,039) received no additional DNR. Noninferiority in event-free survival (EFS) and adverse reactions of special interest (ARSI) were investigated.

Key data: The 5-year EFS was 92.5% (standard error [SE], 0.8%) and 92.2% (SE, 0.9%) in the CA and EA, respectively. Cumulative incidence of relapse was 5.8% (SE, 0.7%) for the CA and 5.7% (SE, 0.7%) for the EA. Overall survival (OS) was similar between arms at 97.6% (SE, 0.5%) for the CA and 97.4% (SE, 0.5%) for the EA. ARSI were comparable between groups, but incidence of invasive fungal infections was lower in the EA than in the CA (0.5% vs 1.5%, p = 0.02).

Key learning: Reduced DNR dosing during induction did not affect the outcome of pediatric patients with favorable prognostic factors but did result in a lower rate of invasive fungal infections, suggesting a reduction in infectious toxicity.