As reported in the Journal of Clinical Oncology by Angiolillo et al, findings from the phase III Children’s Oncology Group (COG) AALL0932 trial indicated that “outstanding outcomes” can be achieved with maintenance therapy with a reduced frequency of vincristine/dexamethasone pulses in pediatric patients with average-risk B-cell acute lymphoblastic leukemia (ALL).
Study Details
AALL0932 enrolled 9,298 patients aged 1 to 9.99 years with newly diagnosed National Cancer Institute (NCI) standard-risk B-cell ALL between August 2010 and March 2018, with all patients receiving three-drug induction therapy. Among these, 2,364 patients with average-risk disease were randomly assigned in a 2 × 2 factorial scheme at the start of maintenance therapy to receive vincristine/dexamethasone pulses every 4 weeks (VCR/DEX4; n = 1,186) or every 12 weeks (VCR/DEX12; n = 1,178) and to a starting dose of once weekly oral methotrexate at 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40). The four treatment groups consisted of
- VCR/DEX4 + MTX20 (n = 600)
- VCR/DEX4 + MTX40 (n = 586)
- VCR/DEX12 + MTX20 (n = 586)
- VCR/DEX12 + MTX40 (n = 592).
Key Findings
Among all 9,226 patients with standard-risk B-cell ALL, 5-year event-free survival and overall survival rates from enrollment were 92.0% (95% confidence interval [CI] = 91.1%–92.8%) and 96.8% (95% CI = 96.2%–97.3%).
Among all 2,364 randomly assigned average-risk patients, 5-year disease-free survival and overall survival from the start of maintenance therapy were 94.6% (95% CI = 93.3%–95.9%) and 98.5% (95% CI = 97.7%–99.2%), respectively.
Among average-risk patients, 5-year disease-free survival was 94.1% (95% CI = 92.2%–96.0%) for patients randomly assigned to receive VCR/DEX4 vs 95.1% (95% CI = 93.3%–96.9%) for those assigned to receive VCR/DEX12 (P = .86). Five-year overall survival was 98.3% (95% CI = 97.2%–99.4%) with VCR/DEX4 vs 98.6% (95% CI = 97.7%–99.6%) with VCR/DEX12 (P = .69).
“The [patients with standard-risk/average-risk B-cell] ALL who received VCR/DEX12 had outstanding outcomes despite receiving one-third of the vincristine/dexamethasone pulses previously used as standard of care on COG trials.”— Angiolillo et al
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Among average-risk patients, 5-year disease-free survival was 95.1% (95% CI = 93.3%–96.8%) for patients randomly assigned to receive MTX20 vs 94.2% (95% CI = 92.2%–96.1%) for those assigned to receive MTX40 (P = .92). Five-year overall survival was 98.8% (95% CI = 97.9%–99.7%) with MTX20 vs 98.1% (95% CI = 97.0%–99.2%) with MTX40 (P = .89).
Among the four randomly assigned average-risk treatment groups, 5-year disease-free survival for VCR/DEX4 + MTX20, VCR/DEX4 + MTX40, VCR/DEX12 + MTX20, and VCR/DEX12 + MTX40 was 95.4%, 92.8%, 94.7%, and 95.6% (overall P = .06). Overall survival at 5 years was 98.7%, 97.9%, 98.9%, and 98.4%, respectively (P = .61)
The investigators concluded, “The [patients with standard-risk/average-risk B-cell] ALL who received VCR/DEX12 had outstanding outcomes despite receiving one-third of the vincristine/dexamethasone pulses previously used as standard of care on COG trials. The higher starting dose of MTX [at] 40 mg/m2 once weekly did not improve outcomes when compared with 20 mg/m2 once weekly. The decreased frequency of vincristine/dexamethasone pulses has been incorporated into frontline COG [B-cell] ALL trials to decrease the burden of therapy for patients and their families.”
Anne L. Angiolillo, MD, of the Center for Cancer and Blood Disorders, Children’s National Medical Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by NCI grants, St. Baldrick’s Foundation, and BD Biosciences. For full disclosures of the study authors, visit ascopubs.org.
