Reducing Daunorubicin in Induction Therapy in Children With B-Lineage ALL With Favorable Prognosis: Results of Phase III Trial AIEOP-BFM ALL 2009
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: PURPOSE Modern ALL therapy aims to reduce toxicity, while maintaining and improving the current high cure rates. Acute and late sequelae of anthracyclines are of major concern. The AIEOP-BFM ALL 2009 trial aimed to clarify the need for anthracyclines in low-risk patients. PATIENTS AND METHODS After 2 weeks of induction therapy, which included two daunorubicin (DNR) doses once weekly (30 mg/m 2 each) as part of a 4-drug therapy, patients age 1-17 years with newly diagnosed non–high-risk B-ALL either positive for ETV6::RUNX1 or with rapid treatment response, as assessed by induction day-15 evaluation, were randomly assigned to receive either two additional doses of DNR (control arm [CA]) or no further DNR during induction (experimental arm [EA]). Patients treated as randomly assigned were included in the primary analysis on noninferiority in event-free survival (EFS). Adverse reactions of special interest (ARSI) were analyzed in the as-treated population. RESULTS Of 6,136 patients enrolled in AIEOP-BFM ALL 2009, 2,514 patients (41.0%) were eligible for this random assignment, with 82.7% actually randomly assigned (EA: n = 1,040 and CA: n = 1,039). The 5-year EFS was 92.5% (SE 0.8%) in CA and 92.2% (SE 0.9%) in EA. Accordingly, cumulative incidence of relapse was 5.8% (SE 0.7%) and 5.7% (SE 0.7%), and overall survival was 97.6% (SE 0.5%) and 97.4% (SE 0.5%) in CA and EA, respectively. Life-threatening and fatal ARSI were similar in the two arms, but there was a three times lower incidence of invasive fungal infections in the EA (0.5% v 1.5%, P = .02). CONCLUSION A reduced DNR dose during induction did not compromise the outcome of patients with favorable prognostic factors but did diminish infectious toxicity indicated by the lower rate of invasive fungal infections.
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-25-01357
Authors: Hanna Gottschalk, Anja Möricke, Valentino Conter, Martin Schrappe, Jan Starý, Gunnar Cario, Michael Dworzak, Andishe Attarbaschi, Draga Barbaric, Franco Locatelli, Nicole Bodmer, Sarah Elitzur, Daniela Silvestri, Luciano Dalla-Pozza, Anke Katharina Bergmann, Christian Flotho, Barbara Buldini, Martin Stanulla, Shai Izraeli, Carmelo Rizzari, Jean-Pierre Bourquin, Andrea Biondi, Maria Grazia Valsecchi, Martin Zimmermann
Institutions: University Hospital Schleswig-Holstein, Charles University, University Hospital in Motol, St Anna Children's Hospital, St. Anna Children's Cancer Research Institute, Medical University of Vienna, UNSW Sydney, Sydney Children's Hospital, Università Cattolica del Sacro Cuore, Bambino Gesù Children's Hospital, University Children's Hospital Zurich, Tel Aviv University, Schneider Children's Medical Center, Children's Hospital at Westmead, Westmead Hospital, University of Würzburg, University Medical Center Freiburg, University of Padua, Medizinische Hochschule Hannover
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4416084563