Intermittent vs Intensive PEG-Asparaginase in Pediatric Acute Lymphoblastic Leukemia
In a Scandinavian study reported in the Journal of Clinical Oncology, Albertsen et al found that use of intermittent vs intensive pegylated (PEG)-asparaginase was associated with similar efficacy and reduced asparaginase-related toxicity in pediatric acute lymphoblastic leukemia (ALL).
The study began enrolling children aged 1.0 to 17.9 years with non–high risk ALL in Denmark, Finland, Iceland, Norway, and Sweden in 2008. After induction and consolidation therapy, patients received 5 intramuscular PEG-asparaginase injections (1,000 IU/m2) every 2 weeks, and were then randomly assigned to an additional 3 doses at 6-week intervals (intermittent group, n = 309) or 10 doses at 2-week intervals (control group, n = 316).
The primary endpoint was noninferior (6% margin) disease-free survival in the intermittent group. Toxicity reduction was a secondary endpoint. Randomization was closed in March 2016, with all study patients still in the intensive therapy control group being switched to the intermittent group on the basis of findings in interim analysis.
Efficacy and Toxicity Outcomes
Median follow-up was 4.1 years. Disease-free survival at 5 years was 92.2% in the intermittent group vs 90.8% in the control group, with the noninferiority limit not being exceeded.
The 3-year cumulative incidence of any first asparaginase-related toxicity was 9.3% in the intermittent group vs 18.1% in the control group (P = .001). Among all patients, asparaginase-related toxicities consisted of hypersensitivity in 13, osteonecrosis in 29, pancreatitis in 24, and thromboembolism in 17. The incidence of each was lower in the intermittent group, but significantly so for only pancreatitis (6-month risk, 1.3% vs 5.8%, P = .002). In analysis adjusting for sex and risk group and stratified by age, risk for asparaginase-related toxicity remained significantly lower in the intermittent group (hazard ratio = 0.48, P = .001).
The investigators concluded, “The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-[asparaginase] therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-[asparaginase] therapy.”
Birgitte Klug Albertsen, MD, PhD, of the Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Denmark, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Danish Childhood Cancer Foundation. For full disclosures of the study authors, visit jco.ascopubs.org.
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