TY - JOUR
T1 - Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia
T2 - Results From Children's Oncology Group AALL0932
AU - Angiolillo, Anne L.
AU - Schore, Reuven J.
AU - Kairalla, John A.
AU - Devidas, Meenakshi
AU - Rabin, Karen R.
AU - Zweidler-McKay, Patrick
AU - Borowitz, Michael J.
AU - Wood, Brent
AU - Carroll, Andrew J.
AU - Heerema, Nyla A.
AU - Relling, Mary V.
AU - Hitzler, Johann
AU - Lane, Ashley R.
AU - Maloney, Kelly W.
AU - Wang, Cindy
AU - Bassal, Mylene
AU - Carroll, William L.
AU - Winick, Naomi J.
AU - Raetz, Elizabeth A.
AU - Loh, Mignon L.
AU - Hunger, Stephen P.
N1 - Funding Information:
Supported by grants from National Cancer Institute (NCI) grants to the Children’s Oncology Group (U10 CA98543, U10 CA98413, U10 CA 180886, and U10 CA 180899) and by research funding from St Baldrick’s Foundation and BD Biosciences, and U24 CA114766 (COG Specimen Banking), and Human Specimen Banking in NCI-Sponsored Clinical Trials (1U24-CA196173).
Publisher Copyright:
© 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021/5/1
Y1 - 2021/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85099856294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85099856294&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.00494
DO - 10.1200/JCO.20.00494
M3 - Article
C2 - 33411585
AN - SCOPUS:85099856294
SN - 0732-183X
VL - 39
SP - 1437
EP - 1447
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 13
ER -