Impact of Dosing Interval Adherence on Pharmacokinetic Outcomes of Recombinant Erwinia Asparaginase in Pediatric Leukemia or Lymphoma.

[INTRODUCTION] Treatment for pediatric acute lymphoblastic leukemia includes asparaginase as an integral component of therapy. Hypersensitivity reactions or silent inactivation to Escherichia coli (E. coli) formulations may necessitate switching to Erwinia-based asparaginase (asparaginase Erwinia chrysanthemi [E-ASP] or recombinant asparaginase Erwinia chrysanthemi [R-ASP]). However, pharmacokinetic data for R-ASP in pediatrics remain limited, and recommended dosing schedules present logistical challenges. We investigated if adherence to approved dosing regimens for R-ASP is necessary to achieve optimal pharmacokinetic exposure in pediatric patients with leukemia or lymphoma.

[METHODS] We performed a single institution, retrospective review of pharmacokinetic data in patients who received R-ASP between October 1, 2021 and September 30, 2024. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to evaluate asparaginase pharmacokinetic activity. The pharmacokinetic model was used to determine if the labeled dosing window for R-ASP is required to achieve effective asparagine depletion.

[RESULTS] Twenty-six patients with 115 measurements of serum asparaginase activity (SAA) were included in the analysis. Based on model simulations from our pediatric patient data, maintaining SAA ≥ 0.1 IU/mL in 90% of patients throughout the dosing interval with R-ASP 25/25/50 mg/m administered intramuscularly on Monday, Wednesday, and Friday requires precise timing. Specifically, the Friday 50 mg/m dose must be administered within 58 h of the Wednesday morning dose to sustain therapeutic activity. Additionally, only 62.5% of patients maintained SAA ≥ 0.1 IU/mL at 72 h after the last dose with R-ASP 25 mg/m administered intramuscularly on a Monday, Wednesday, and Friday dosing schedule.

[CONCLUSION] Overall, our findings support the importance of adhering closely to the United States Food and Drug Administration approved dosing schedule for R-ASP to ensure adequate asparaginase activity in pediatric patients with leukemia or lymphoma.