Anthracycline-free protocol for favorable-risk childhood ALL: A noninferiority comparison between Malaysia-Singapore ALL 2003 and ALL 2010 studies
Document Type
Article
Publication Date
7-1-2023
Abstract
PURPOSETo investigate whether, for children with favorable-risk B-cell precursor ALL (BCP-ALL), an anthracycline-free protocol is noninferior to a modified Berlin-Frankfurt-Muenster ALL-IC2002 protocol, which includes 120 mg/m2 of anthracyclines.PATIENTS AND METHODSThree hundred sixty-nine children with favorable-risk BCP-ALL (age 1-9 years, no extramedullary disease, and no high-risk genetics) who cleared minimal residual disease (& LE;0.01%) at the end of remission induction were enrolled into Ma-Spore (MS) ALL trials. One hundred sixty-seven standard-risk (SR) patients (34% of Malaysia-Singapore ALL 2003 study MS2003]) were treated with the MS2003-SR protocol and received 120 mg/m2 of anthracyclines during delayed intensification while 202 patients (42% of MS2010) received an anthracycline-free successor protocol. The primary outcome was a noninferiority margin of 1.15 in 6-year event-free survival (EFS) between the MS2003-SR and MS2010-SR cohorts.RESULTSThe 6-year EFS of MS2003-SR and MS2010-SR (anthracycline-free) cohorts was 95.2% & PLUSMN; 1.7% and 96.5% & PLUSMN; 1.5%, respectively (P = .46). The corresponding 6-year overall survival was 97.6% and 99.0% & PLUSMN; 0.7% (P = .81), respectively. The cumulative incidence of relapse was 3.6% and 2.6%, respectively (P = .42). After adjustment for race, sex, age, presenting WBC, day 8 prednisolone response, and favorable genetic subgroups, the hazard ratio for MS2010-SR EFS was 0.98 (95% CI, 0.84 to 1.14; P = .79), confirming noninferiority. Compared with MS2003-SR, MS2010-SR had significantly lower episodes of bacteremia (30% v 45.6%; P = .04) and intensive care unit admissions (1.5% v 9.5%; P = .004).CONCLUSIONIn comparison with MS2003-SR, the anthracycline-free MS2010-SR protocol is not inferior and was less toxic as treatment for favorable-risk childhood BCP-ALL.
Keywords
Anthracyclines, Antibiotics, Antineoplastic, Antineoplastic combined chemotherapy protocols, Child, Child, Preschool, Disease-free survival, Humans, Infant, Malaysia, Neoplasm recurrence, Local, Precursor cell lymphoblastic leukemia-lymphoma, Singapore, Treatment outcome
Divisions
paediatrics
Funders
Kementerian Sains, Teknologi dan Inovasi [Grant no. IF1019Q1148, RP049-17/HTM],A.E.J.Y. Singapore National Medical Research Council [Grant no. NMRC/CSA/0053/2008, NMRC/CSA/0053/2013],National University of Singapore [Grant no. NMRC/CG/NCIS/2010]
Publication Title
Journal of Clinical Oncology
Volume
41
Issue
20
Publisher
Wolters Kluwer Health
Publisher Location
TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA