Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932

Anne L. Angiolillo, Reuven J. Schore, John A. Kairalla, Meenakshi Devidas, Karen R. Rabin, Patrick Zweidler-McKay, Michael J. Borowitz, Brent Wood, Andrew J. Carroll, Nyla A. Heerema, Mary V. Relling, Johann Hitzler, Ashley R. Lane, Kelly W. Maloney, Cindy Wang, Mylene Bassal, William L. Carroll, Naomi J. Winick, Elizabeth A. Raetz, Mignon L. LohStephen P. Hunger

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

PURPOSE AALL0932 evaluated two randomized maintenance interventions to optimize disease-free survival (DFS) while reducing the burden of therapy in children with newly diagnosed NCI standard-risk (SR) B-acute lymphoblastic leukemia (B-ALL). METHODS AALL0932 enrolled 9,229 patients with B-ALL; 2,364 average-risk (AR) patients were randomly assigned (2 3 2 factorial design) at the start of maintenance therapy to vincristine/dexamethasone pulses every 4 (VCR/DEX4) or every 12 (VCR/DEX12) weeks, and a starting dose of once weekly oral methotrexate of 20 mg/m2 (MTX20) or 40 mg/m2 (MTX40). RESULTS Five-year event-free survival and overall survival (OS) from enrollment, for all eligible and evaluable SR B-ALL patients (n=9,226), were 92.0% (95% CI, 91.1% to 92.8%) and 96.8% (95% CI, 96.2% to 97.3%), respectively. The 5-year DFS and OS fromthe start ofmaintenance for randomly assigned AR patients were 94.6% (95% CI, 93.3% to 95.9%) and 98.5% (95% CI, 97.7% to 99.2%), respectively. The 5-year DFS and OS for patients randomly assigned to receive VCR/DEX4 (n=1,186) versus VCR/DEX12 (n=1,178) were 94.1% (95% CI, 92.2% to 96.0%) and 98.3%(95%CI, 97.2%to 99.4%) v 95.1%(95%CI, 93.3%to 96.9%) and 98.6% (95% CI, 97.7% to 99.6%), respectively (P=.86 and .69). The 5-year DFS and OS for AR patients randomly assigned to receive MTX20 versus MTX40 were 95.1% (95%CI, 93.3% to 96.8%) and 98.8% (95%CI, 97.9% to 99.7%) versus 94.2% (95% CI, 92.2% to 96.1%) and 98.1% (95% CI, 97.0% to 99.2%), respectively (P=.92 and .89). CONCLUSIONS The NCI-SR AR B-ALL who received VCR/DEX12 had outstanding outcomes despite receiving one third of the vincristine/dexamethasone pulses previously used as standard of care on Children's Oncology Group (COG) trials. The higher starting dose of MTX of 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-ALL trials to decrease the burden of therapy for patients and their families.

Original languageEnglish (US)
Pages (from-to)1437-1447
Number of pages11
JournalJournal of Clinical Oncology
Volume39
Issue number13
DOIs
StatePublished - May 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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