PK model predicts peg-asparaginase inactivation in ALL

Results from a Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 study analyzing asparaginase enzyme activity (AEA) pharmacokinetics in 644 patients aged 1–45 years with acute lymphoblastic leukemia (ALL) were recently published in the British Journal of Haematology by Dam et al. The study included 3,003 AEA samples collected 14 days post polyethylene glycol (peg)-asparaginase doses, with additional sampling between doses from February 2017 to December 2022 across Nordic and Baltic countries.

Key data: The incidence of inactivation was 15.2%. Mean AEA trough concentration (Ctrough) after the initial dose was significantly lower in patients with subsequent inactivation vs those without inactivation (79 international units per liter [iu/L] vs 174 iu/L; p < 0.001). The pharmacokinetic (PK) model demonstrated 87.8% sensitivity and 65.5% specificity for detecting increased peg-asparaginase clearance over time in patients experiencing inactivation.

Key learning: A validated PK model can identify increased clearance preceding inactivation in patients with ALL treated with intramuscular peg-asparaginase, enabling potential early intervention before clinical manifestation of hypersensitivity reactions and treatment failure.