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Medline ® Abstract for Reference 19

of 'Overview of the treatment of acute lymphoblastic leukemia in children and adolescents'

Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4.
Angiolillo AL, Schore RJ, Devidas M, Borowitz MJ, Carroll AJ, Gastier-Foster JM, Heerema NA, Keilani T, Lane AR, Loh ML, Reaman GH, Adamson PC, Wood B, Wood C, Zheng HW, Raetz EA, Winick NJ, Carroll WL, Hunger SP
J Clin Oncol. 2014;32(34):3874. Epub 2014 Oct 27.
PURPOSE: Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL.
PATIENTS AND METHODS: A total of 165 evaluable patients were randomly assigned at a 2:1 ratio to receive SC-PEG at 2,100 (SC-PEG2100; n = 69) or 2,500 IU/m(2) (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m(2) (SS-PEG2500; n = 54) as part of an otherwise identical chemotherapy regimen. The groups were similar demographically, except more female patients received SC-PEG2500.
RESULTS: The mean half-life of plasma asparaginase activity for both SC-PEG doses was approximately 2.5×longer than that of SS-PEG2500. The total systemic exposure, as defined by induction area under the curve from time 0 to 25 days, was greater with SC-PEG2500 than with SS-PEG2500 or SC-PEG2100. The proportion of patients with plasma asparaginase activity≥100 mIU/mL and≥400 mIU/mL was higher in patients who received SC-PEG as compared with SS-PEG2500. After one dose of pegylated asparaginase on induction day 4, plasma asparagine was undetectable for 11 days for SS-PEG2500 and 18 days for both SC-PEG groups.
CONCLUSION: SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500 and has a comparable toxicity profile in children with HR B-cell ALL.
Anne L. Angiolillo, Reuven J. Schore, Ashley R. Lane, and Gregory H. Reaman, Children's National Medical Center, Washington, DC; Meenakshi Devidas, Colleges of Medicine, Public Health and Health Professions, University of Florida; Charlotte Wood and Hao W. Zheng, Children's Oncology Group, Gainesville, FL; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore; Taha Keilani, Sigma-Tau Pharmaceuticals, Gaithersburg, MD; Andrew J. Carroll, University of Alabama at Birmingham, Birmingham, AL; Julie M. Gastier-Foster and Nyla A. Heerema, Ohio State University Wexner Medical Center; Julie M. Gastier-Foster, Ohio State University College of Medicine and Nationwide Children's Hospital, Columbus, OH; Mignon L. Loh, University of California at San Francisco, San Francisco, CA; Peter C. Adamson, Children's Hospital of Philadelphia, Philadelphia, PA; Brent Wood, University of Washington, Seattle, WA; Elizabeth A. Raetz and William L. Carroll, New York University Cancer Institute, New