pegaspargase

Pegaspargase is a pegylated form of the enzyme L-asparaginase used in the chemotherapy of acute lymphoblastic leukemia (ALL) and some lymphoid malignancies. By attaching polyethylene glycol (PEG) to the enzyme, pegylation increases the circulating half-life and can reduce immediate immunogenicity, allowing less frequent dosing than unmodified L-asparaginase. It is marketed under the brand name Oncaspar and is used as part of multi-agent regimens.

Mechanism of action: Pegaspargase depletes circulating asparagine by converting it to aspartic acid and ammonia. Leukemic cells often cannot synthesize sufficient asparagine, making them dependent on extracellular stores; depletion of asparagine inhibits protein synthesis and causes cell death, while many normal cells tolerate the depletion better.

Administration and dosing: Pegaspargase is given by intramuscular or intravenous injection. Its longer half-life compared with native L-asparaginase allows dosing every two weeks in many ALL regimens, in combination with other chemotherapy agents. Dosing is typically guided by body surface area, with adjustments for toxicity and clinical response.

Adverse effects and monitoring: Common risks include hypersensitivity reactions and anaphylaxis, pancreatitis, hepatotoxicity with elevated liver enzymes, and coagulopathies that can cause bleeding or thrombosis. Other potential events include hyperglycemia, hyperlipidemia, and transient reductions in protein synthesis. Monitoring often includes liver function tests, coagulation studies, amylase/lipase for pancreatitis, and, when available, serum asparaginase activity to confirm therapeutic levels.

Regulatory status and notes: Pegaspargase is approved in many countries for use as part of ALL treatment protocols. Patients are monitored closely for allergic reactions and organ toxicity, and live vaccines are generally avoided during treatment.