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Sporadic PEG-Asparaginase Dosing Reduces Treatment-Related Toxicity in ALL
Following the first 5 doses of treatment, intermittent pegylated-asparaginase (PEG-asp) effectively reduces toxicity compared with continuous PEG-asp in pediatric patients with acute lymphoblastic leukemia (ALL), results from a recent study show (J Clin Oncol. 2019 Apr 12. Epub ahead of print).
“Asparaginase is an essential drug in childhood…[ALL]…therapy and is frequently given for months to obtain continuous asparagine depletion,” said Birgitte Klug Albertsen, MD, PhD, Children and Adolescent Health, Aarhus University Hospital, Denmark, and colleagues.
“We randomly assigned patients to continuous versus intermittent…PEG-asp…treatment, hypothesizing there would be decreased toxicity with unchanged efficacy,” they explained.
The study examined 625 pediatric patients (median age, 4.2 years) being treated for non–high-risk ALL. The patients received 5 intramuscular PEG-asp injections (1,000 IU/m2) every 2 weeks and were then randomly assigned to receive an additional 3 doses at 6-week intervals (experimental arm, n = 309) or 10 doses at 2-week intervals (standard arm, n = 316).
The primary end point of the study was noninferior disease-free survival (DFS). The secondary end points included reduced toxicity.
The 5-year DFS was 92.2% (95% CI, 88.6-95.8) in the experimental arm and 90.8% (95% CI, 87.0-94.6) in the standard arm. The 3-year cumulative incidences of any first asparaginase-associated toxicities were 9.3% and 18.1%, respectively (P = .001). Asparaginase-associated toxicities included hypersensitivity (n = 13), osteonecrosis (n = 29), pancreatitis (n = 24), and thromboembolism (n = 17).
In sex- and risk-group–adjusted Cox regression analyses stratified by age (≥10 and <10 years), a reduction in asparaginase-associated toxicity was confirmed (hazard ratio, 0.48; P = .001). Incidence rates of all 4 toxicities were the lowest in the experimental arm, with a significant reduction observed for pancreatitis (6-month risk, 5.8% for the standard arm vs 1.3% for the experimental arm; P = .002).
“The excellent cure rates and reduced toxicity risk support the use of intermittent PEG-asp therapy after the first 10 weeks in future childhood ALL trials that apply prolonged PEG-asp therapy,” Dr Albertsen and colleagues concluded.—Janelle Bradley
