Reducing daunorubicin in induction therapy in children with low-risk B-lineage ALL in the multinational phase 3 AIEOP-BFM ALL 2009 trial

Modern ALL therapy aims to reduce toxicity, while maintaining and improving cure rates. In the multinational phase 3 AIEOP-BFM ALL 2009 trial, childeren with low-risk B-lineage ALL were randomized after two weeks of induction therapy, which included two daunoubicin (DNR) doses once weekly as part of a 4-drug therapy, to either two additional DNR doses (control arm; CA; n=1039) or no further DNR during induction (experimental arm; EA; n=1040). The 5-year event-free survival rate was 92.5% (SE 0.8%) in CA and 92.2% (SE 0.9%) in EA. Five-year cumulative incidence of relapse was 5.8% (SE 0.7%) and 5.7% (SE 0.7%) and overall survival rate was 97.6% (SE 0.5%) and 97.4% (SE 0.5%) in CA and EA, respectively. Life-threatening and fatel adverse reaction of special interest were similar in the two arms, but there was a lower incidence of invasive fungal infections in the EA (0.5% versus 1.5%; p=0.02). The authors conclude that a reduced DNR dose during induction did not compromise the outcome in this patient group but did diminish infectious toxicity.