Plasma asparaginase activity and asparagine depletion in acute lymphoblastic leukemia patients treated with pegaspargase on Children’s Oncology Group AALL07P4^*

Abstract

The efficacy of asparaginase in acute lymphoblastic leukemia (ALL) is dependent on depletion of asparagine, an essential amino acid for ALL cells. The target level of plasma asparaginase activity to achieve asparagine depletion has been between 0.05 and 0.4 IU/mL. COG AALL07P4 examined the asparaginase activity and plasma and CSF asparagine concentration of pegaspargase when given intravenously in the treatment of NCI high risk ALL. Matched plasma asparaginase/asparagine levels of the clearance of 54 doses of pegaspargase given in induction or consolidation demonstrated that all patients who had a plasma asparaginase level >0.02 IU/mL had undetectable plasma asparagine. No difference was observed in CSF asparagine levels associated with matched plasma asparaginase levels of 0.02–0.049 versus 0.05–0.22 IU/mL (p = .25). Our data suggest that a plasma asparaginase activity level of 0.02 IU/mL can effectively deplete plasma asparagine. The data also indicate that the 95% CI for plasma asparagine depletion after a pegaspargase dose is 22–29 days.

Clinical trial registration: clinicaltrials.gov identifier NCT00671034.

Keywords:

• Lymphoid Leukemia
• asparaginase
• asparagine depletion
• pharmacokinetics
• pharmacodynamics

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2018.1542146

Additional information

Funding

This work was supported by grants from National Cancer Institute to the Children’s Oncology Group [U10 CA98543, U10 CA98413, U10 180886, U10 CA180899] and by research funding from Enzon Inc., and Sigma-Tau Pharmaceuticals.