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

Anne L. Angiolillo, Reuven J. Schore, Meenakshi Devidas, Michael J Borowitz, Andrew J. Carroll, Julie M. Gastier-Foster, Nyla A. Heerema, Taha Keilani, Ashley R. Lane, Mignon L. Loh, Gregory H. Reaman, Peter C. Adamson, Brent Wood, Charlotte Wood, Hao W. Zheng, Elizabeth A. Raetz, Naomi J. Winick, William L. Carroll, Stephen P. Hunger

Research output: Contribution to journalArticle

Abstract

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/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (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 2.5x 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.

Original languageEnglish (US)
Pages (from-to)3874-3882
Number of pages9
JournalJournal of Clinical Oncology
Volume32
Issue number34
DOIs
StatePublished - Dec 1 2014

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Asparaginase
Succinic Acid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pharmacokinetics
Escherichia coli
Therapeutics
Asparagine
calaspargase pegol
B-Lymphocytes
Carbamates
Area Under Curve
Half-Life

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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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, Anne L.; Schore, Reuven J.; Devidas, Meenakshi; Borowitz, Michael J; Carroll, Andrew J.; Gastier-Foster, Julie M.; Heerema, Nyla A.; Keilani, Taha; Lane, Ashley R.; Loh, Mignon L.; Reaman, Gregory H.; Adamson, Peter C.; Wood, Brent; Wood, Charlotte; Zheng, Hao W.; Raetz, Elizabeth A.; Winick, Naomi J.; Carroll, William L.; Hunger, Stephen P.

In: Journal of Clinical Oncology, Vol. 32, No. 34, 01.12.2014, p. 3874-3882.

Research output: Contribution to journalArticle

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 2014, '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', Journal of Clinical Oncology, vol. 32, no. 34, pp. 3874-3882. https://doi.org/10.1200/JCO.2014.55.5763
Angiolillo, Anne L. ; Schore, Reuven J. ; Devidas, Meenakshi ; Borowitz, Michael J ; Carroll, Andrew J. ; Gastier-Foster, Julie M. ; Heerema, Nyla A. ; Keilani, Taha ; Lane, Ashley R. ; Loh, Mignon L. ; Reaman, Gregory H. ; Adamson, Peter C. ; Wood, Brent ; Wood, Charlotte ; Zheng, Hao W. ; Raetz, Elizabeth A. ; Winick, Naomi J. ; Carroll, William L. ; Hunger, Stephen P. / 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. In: Journal of Clinical Oncology. 2014 ; Vol. 32, No. 34. pp. 3874-3882.
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abstract = "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/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (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 2.5x 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.",
author = "Angiolillo, {Anne L.} and Schore, {Reuven J.} and Meenakshi Devidas and Borowitz, {Michael J} and Carroll, {Andrew J.} and Gastier-Foster, {Julie M.} and Heerema, {Nyla A.} and Taha Keilani and Lane, {Ashley R.} and Loh, {Mignon L.} and Reaman, {Gregory H.} and Adamson, {Peter C.} and Brent Wood and Charlotte Wood and Zheng, {Hao W.} and Raetz, {Elizabeth A.} and Winick, {Naomi J.} and Carroll, {William L.} and Hunger, {Stephen P.}",
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TY - JOUR

T1 - Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia

T2 - Results from children's oncology group study AALL07P4

AU - Angiolillo, Anne L.

AU - Schore, Reuven J.

AU - Devidas, Meenakshi

AU - Borowitz, Michael J

AU - Carroll, Andrew J.

AU - Gastier-Foster, Julie M.

AU - Heerema, Nyla A.

AU - Keilani, Taha

AU - Lane, Ashley R.

AU - Loh, Mignon L.

AU - Reaman, Gregory H.

AU - Adamson, Peter C.

AU - Wood, Brent

AU - Wood, Charlotte

AU - Zheng, Hao W.

AU - Raetz, Elizabeth A.

AU - Winick, Naomi J.

AU - Carroll, William L.

AU - Hunger, Stephen P.

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (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 2.5x 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.

AB - 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/m2 (SC-PEG2500; n = 42) versus SS-PEG 2,500 IU/m2 (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 2.5x 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.

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