Impact of Asparaginase Discontinuation on Outcome in Childhood Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. ASNase ( ) substitution was approved in 2011 for allergic reactions. has, however, been intermittently unavailable because of drug supply issues. The impact...

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Bibliographic Details
Published in:Journal of clinical oncology Vol. 38; no. 17; p. 1897
Main Authors: Gupta, Sumit, Wang, Cindy, Raetz, Elizabeth A, Schore, Reuven, Salzer, Wanda L, Larsen, Eric C, Maloney, Kelly W, Mattano, Jr, Len A, Carroll, William L, Winick, Naomi J, Hunger, Stephen P, Loh, Mignon L, Devidas, Meenakshi
Format: Journal Article
Language:English
Published: United States 10.06.2020
Subjects:
Adolescent
Asparaginase - administration & dosage
Asparaginase - adverse effects
Asparaginase - supply & distribution
Child
Child, Preschool
Disease-Free Survival
Erwinia - enzymology
Female
Humans
Infant
Male
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - adverse effects
Polyethylene Glycols - supply & distribution
Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy
Prognosis
Randomized Controlled Trials as Topic
Substance Withdrawal Syndrome - etiology
Treatment Outcome
ISSN:1527-7755, 1527-7755
Online Access:Get more information
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Summary:Asparaginase (ASNase) is an important component of acute lymphoblastic leukemia (ALL) treatment, but is often discontinued because of toxicity. ASNase ( ) substitution was approved in 2011 for allergic reactions. has, however, been intermittently unavailable because of drug supply issues. The impact of substitution or complete ASNase discontinuation is unknown. Patients aged 1-30.99 years in frontline Children's Oncology Group trials for B-cell acute lymphoblastic leukemia between 2004 and 2011 (National Cancer Institute [NCI] standard risk [SR]: AALL0331; NCI high risk: AALL0232) were included. The number of prescribed pegaspargase (PEG-ASNase) doses varied by trial and strata. Maintenance therapy did not contain ASNase. Landmark analyses at maintenance compared disease-free survival (DFS) among those receiving all prescribed PEG-ASNase doses versus switching to but receiving all doses versus not receiving all ASNase doses. We included 5,195 AALL0331 and 3,001 AALL0232 patients. The cumulative incidence of PEG-ASNase discontinuation was 12.2% ± 4.6% in AALL0331 and 25.4% ± 0.8% in AALL0232. In multivariable analyses, NCI high-risk patients not receiving all prescribed ASNase doses had inferior DFS (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.9; = .002) compared with those receiving all prescribed PEG-ASNase doses. Patients with substitution who completed subsequent courses were not at increased risk (HR, 1.1; 95% CI, 0.7 to 1.6; = .69). NCI SR patients who discontinued ASNase were not at elevated risk (HR, 1.2; 95% CI, 0.9 to 1.6; = .23), except when restricted to those with slow early response, who were prescribed more ASNase because of therapy intensification (HR, 1.7; 95% CI, 1.1 to 2.7; = .03). Discontinuation of ASNase doses is associated with inferior DFS in higher-risk patients. Our results illustrate the severe consequences of shortages.
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ISSN:1527-7755
1527-7755
DOI:10.1200/JCO.19.03024