In an analysis from the Children’s Oncology Group (COG) AALL0331 trial reported in the Journal of Clinical Oncology, Mattano et al found that the addition of pegaspargase intensification did not improve the high rate of continuous complete remission achieved with a standard COG low-intensity chemotherapy backbone in children with low-risk B-cell acute lymphoblastic leukemia (ALL), including those with favorable cytogenetics.
Study Details
The AALL0331 trial enrolled 5,377 patients with standard-risk B-cell ALL (aged 1–9 years, white blood cell count < 50,000/µL) between 2005 and 2010. After receiving a common three-drug induction regimen, a cohort of 1,857 patients were included in the low-risk B-cell ALL random assignment component of the trial. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics consisting of ETV6-RUNX1 fusion or simultaneous trisomies of chromosomes 4, 10, and 17.
The low-risk patients were randomly assigned to receive standard COG low-intensity therapy (including one pegaspargase dose during induction and one during delayed intensification) with (n = 928) or without (n = 929) four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year continuous complete remission rate from 92% to 96% with the addition of pegaspargase intensification. Overall, ETV6-RUNX1 fusion was present in 1,139 patients (61.3%), triple trisomy in 712 (38.3%), and both in 6 (0.3%).
Standard COG therapy without intensified pegaspargase, which can easily be given [on an outpatient basis] with limited toxicity, cures nearly all children with [B-cell] ALL identified as low-risk by clinical, early response and favorable cytogenetic criteria.— Mattano et al
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Key Findings
Continuous complete remission and overall survival at 6 years in the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%.
The 6-year continuous complete remission rate was 95.3% ± 0.8% in the intensified pegaspargase group vs 94.0% ± 0.8% in the standard therapy group (P = .13). The 6-year overall survival rate was 98.1% ± 0.5% vs 99.2% ± 0.3% (P = .99).
Compared with a cohort of 422 standard-risk patients in AALL0331 who met all low-risk criteria but had neither favorable nor unfavorable cytogenetics and received standard therapy, the standard therapy low-risk group had significantly better 6-year continuous complete remission (94.0% ± 0.8% vs 88.6% ± 1.7%; hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.34–2.85, P = .0004) and 6-year overall survival (99.2% ± 0.3% vs 96.1% ± 1.0%, HR = 5.42, 95% CI = 2.37–12.39, P < .0001).
The investigators concluded, “Standard COG therapy without intensified pegaspargase, which can easily be given [on an outpatient basis] with limited toxicity, cures nearly all children with [B-cell] ALL identified as low-risk by clinical, early response and favorable cytogenetic criteria.”
Leonard A. Mattano, Jr, MD, c/o Children’s Oncology Group, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. For full disclosures of the study authors, visit ascopubs.org.
