Pediatric patients with standard-risk (SR) B-cell acute lymphoblastic leukemia (ALL) may not experience improved clinical outcomes with intensified postinduction therapy, according to results from the Children’s Oncology Group (COG) AALL0331 randomized phase 3 trial (ClinicalTrials.gov Identifier: NCT01190930) published in the Journal of Clinical Oncology.
Intensified postinduction therapy improved survival in pediatric patients with high-risk ALL, so COG AALL0331 assessed whether improvements could be achieved in patients with SR disease.
Between 2005 and 2010, 5377 patients were enrolled, and all patients underwent induction with dexamethasone, vincristine, and pegaspargase (PEG). Following induction, patients were classified as SR low, SR average, or SR high, and children with SR-average ALL were randomly assigned to undergo either standard-of-care 4-week consolidation (SC) or 8-week intensified augmented Berlin-Frankfurt-Münster (BFM) consolidation (IC). Children with SR-high ALL were nonrandomly assigned to the full COG-augmented BFM regimen, which included 2 interim maintenance and delayed intensification phases.
For all patients enrolled in AALL0331, median 6-year event-free survival was 88.96%, and 6-year overall survival (OS) was 95.54%.
In children with SR-average ALL, median 6-year continuous complete remission (CCR) was 87.8% in the SC arm and 89.1% in the IC arm (P =.52). In these patients, median 6-year OS was 95.8% in the SC arm and 95.2% in the IC arm (P =1.0).
Patients with SR-average disease with end-induction measurable residual disease (MRD) of 0.01% to less than 0.1% had worse 6-year CCR compared with patients with lower MRD and no improvement with IC.
In the 635 nonrandomly assigned patients with SR-high disease, median 6-year CCR was 85.55% and median 6-year OS was 92.97%.
Of note, the 6-year OS rate for the entire cohort of pediatric patients with SR ALL exceeded 95%. The addition of IC to the therapeutic regimen of patients with SR-average disease did not improve either CCR or OS.
“Taken together, these results suggest that further intensifying conventional therapy will not improve cure rates and that novel approaches are needed,” co ncluded the researchers.
- Maloney KW, Devidas M, Wang C, et al. Outcome in children with standard-risk b-cell acute lymphoblastic leukemia: results of Children’s Oncology Group Trial AALL0331 [published online December 11, 2019]. J Clin Oncol. doi:10.1200/JCO.19.01086