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, Mylène Bassal, William L Carroll, Naomi J Winick, Elizabeth A Raetz, Mignon L Loh, Stephen P Hunger, 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, Mylène Bassal, William L Carroll, Naomi J Winick, Elizabeth A Raetz, Mignon L Loh, Stephen P Hunger
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 × 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 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 (with 95% CIs), for all eligible and evaluable SR B-ALL patients (n = 9,226), were 92.0% (91.1% and 92.8%) and 96.8% (96.2% and 97.3%), respectively. The 5-year DFS and OS from the start of maintenance for randomly assigned AR patients were 94.6% (93.3% and 95.9%) and 98.5% (97.7% and 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% (92.2% and 96.0%) and 98.3% (97.2% and 99.4%) v 95.1% (93.3% and 96.9%) and 98.6% (97.7% and 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% (93.3% and 96.8%) and 98.8% (97.9% and 99.7%) v 94.2% (92.2% and 96.1%) and 98.1% (97.0% and 99.2%), respectively (P = .92 and .89).
Conclusions: The 0NCI-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/week did not improve outcomes when compared with 20 mg/m2/week. 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.
Trial registration: ClinicalTrials.gov NCT01190930.
Conflict of interest statement
Anne L. AngiolilloHonoraria: Servier PharmaceuticalsTravel, Accommodations, Expenses: Servier Pharmaceuticals Reuven J. SchoreResearch Funding: Janssen Research & Development, Amgen John A. KairallaStock and Other Ownership Interests: Johnson & Johnson Meenakshi DevidasHonoraria: PSI, Novartis Patrick Zweidler-McKayStock and Other Ownership Interests: Immunogen Michael J. BorowitzConsulting or Advisory Role: AmgenResearch Funding: Becton DickinsonTravel, Accommodations, Expenses: Beckman Coulter Brent WoodHonoraria: Amgen, Seattle Genetics, Abbvie, Janssen, Astellas PharmaConsulting or Advisory Role: SysmexResearch Funding: Amgen, Seattle Genetics, Pfizer, Juno Therapeutics, BiolineRx, Biosight, Stemline Therapeutics, Janssen Oncology, NovartisTravel, Accommodations, Expenses: Amgen Mary V. RellingResearch Funding: Servier Pharmaceutical Elizabeth A. RaetzResearch Funding: PfizerOther Relationship: Celgene Mignon L. LohConsulting or Advisory Role: MediSix Therapeutics Stephen P. HungerStock and Other Ownership Interests: Amgen, MerckHonoraria: AmgenConsulting or Advisory Role: NovartisNo other potential conflicts of interest were reported.
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Source: PubMed