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/m2 administered intramuscularly on Monday, Wednesday, and Friday requires precise timing. Specifically, the Friday 50 mg/m2 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/m2 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.