Scientific Poster Session III - Research Fellowship Platform

Abstract

Contemporary treatment for pediatric acute lymphoblastic leukemia incorporates long-acting asparaginase as a cornerstone of therapy. Patients who develop hypersensitivity reactions (HSR) or silent inactivation to these formulations may benefit from transitioning to Erwinia-based asparaginase (Erwinia asparaginase chrysanthemi, E-ASP or recombinant Erwinia asparaginase, R-ASP). However, pharmacokinetic and toxicity data on R-ASP in the pediatric population is limited.

Research Question or Hypothesis:

We hypothesize that the pharmacokinetic and toxicity profiles of R-ASP are comparable to those of E-ASP in pediatric patients with leukemia.

Study Design:

We performed a single institution, retrospective review of the pharmacokinetics and toxicities in patients who received R-ASP from October 1, 2021 to September 30, 2023. Pharmacokinetic data were compared to published controls with E-ASP and R-ASP.

Methods:

The primary objective was to determine the median duration of asparaginase activity above 0.1 IU/mL following a single dose of 25 mg/m² of R-ASP. A one-compartment model with first-order absorption and elimination was used to fit pharmacokinetic data. Population and individual post-hoc data were estimated using non-linear mixed effects modeling analysis. Clinical toxicities (i.e., HSR, pancreatitis, hyperglycemia, hypertriglyceridemia, and venous thromboembolism (VTE)) were recorded up to one week post-dose and graded according to CTCAE v4.0.

Results:

We identified 24 individuals with 110 serum measurements of asparaginase activity. The median duration of activity above 0.1 IU/mL was 3.4 days for R-ASP compared to 4 days for E-ASP. The most common attributable toxicities in 32 individuals receiving 449 doses of R-ASP were HSR (15.6%, Grade 1), hypertriglyceridemia (9.4%, Grade 3 and 4), pancreatitis (9.4%, Grade 2), and VTE (6.3%, Grade 2).

Conclusion:

Compared to published controls with E-ASP and R-ASP, our cohort demonstrated a shorter median duration of asparaginase activity above 0.1 IU/mL. The occurrence of subclinical HSR following R-ASP may suggest potential silent inactivation, indicating that additional monitoring of asparaginase activity throughout treatment may be warranted.

Presenting Author

Authors