(008) An Evaluation of the Relationship Between Asparaginase Dose, Pharmacokinetics, and Toxicities Among Pediatric Acute Lymphoblastic Leukemia and Lymphoma Patients

Poster Abstract: Since the 1970s, asparaginase has been credited with the prolongation of event-free survival and an increase in disease-free survival in pediatric patients with acute lymphoblastic leukemia (ALL). Asparaginase remains an important backbone of treatment in pediatric ALL and acute lymphoblastic lymphoma (LLy). However, there are many serious adverse drug reactions associated with asparaginase products. The most frequently reported include hypersensitivity and/or infusion reactions, pancreatitis, hyperglycemia, hyperlipidemia, hepatotoxicity, osteonecrosis, thrombosis, and bleeding events.

Concerns associated with the toxicity profile of asparaginase products have led to discussions regarding the maximum dose of asparaginase that should be administered to pediatric patients. Historically, the Children’s Oncology Group (COG) protocols for B-cell and T-cell leukemia support using a dose of 2,500 units/m2, without a maximum dose. Several adult studies and protocols support capping the asparaginase dose at 3,750 units and have demonstrated improved disease-free and overall survival. Additional adult studies with non-capped doses showed increased adverse events, specifically hepatotoxicity. Serum asparaginase activity (SAA) levels for monitoring the efficacy of asparaginase depletion are institution-specific and are not protocolized through COG. Currently in pediatric patients, it is recommended that SAA levels be strongly considered if asparaginase doses are capped.

The objective was to evaluate the incidence of adverse drug reactions for patients who received a capped dose of asparaginase at 3,750 units compared to patients who received a non-capped dose, and then determine if a correlation exists between dosing strategies, adverse drug reactions, and SAA levels.

This was a single-center, retrospective analysis including patients 1-21 years old who received pegaspargase or calaspargase pegol as part of ALL or LLy therapy at the University of North Carolina Medical Center between July 2019 and July 2023. The primary outcome was the incidence of treatment-related adverse drug reactions for patients who received a capped dose of asparaginase at 3,750 units compared to patients who received a non-capped dose. Secondary outcomes included determining if a correlation is present between adverse drug reactions and SAA levels, and the incidence of relapse-free survival for patients whose asparaginase was capped at a dose of 3,750 units versus non-capped. Pertinent laboratory values indicating an adverse drug reaction to asparaginase products were collected for four weeks following each dose and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. A subgroup analysis was performed to capture the rate of adverse events in patients receiving pegaspargase compared to calaspargase pegol.

Results pending.

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