Pegaspargase (pegylated L-asparaginase) — Drug Monograph

Brand names: Oncaspar

Drug class: Other

Mechanism of Action

A pegylated form of E. coli L-asparaginase in which the enzyme is covalently conjugated to monomethoxypolyethylene glycol. Like native asparaginase, it hydrolyzes circulating L-asparagine, depleting the amino acid that asparagine synthetase–deficient lymphoblasts require for protein synthesis, causing leukemic cell death. PEGylation prolongs half-life (allowing less frequent dosing) and reduces immunogenicity compared with the native enzyme.

FDA Indications

• Acute lymphoblastic leukemia (ALL) — first-line treatment as a component of multi-agent chemotherapy
• Acute lymphoblastic leukemia (ALL) — in patients who have developed hypersensitivity to native E. coli asparaginase

Common Side Effects

• Hypersensitivity reactions
• Nausea/vomiting
• Elevated liver enzymes/hyperbilirubinemia
• Hyperglycemia
• Fatigue
• Fever
• Abnormal clotting parameters

Clinical Pearl

Pegaspargase has largely replaced native E. coli asparaginase in frontline ALL because PEGylation extends its half-life (dosing roughly every 2 weeks instead of multiple times weekly) and lowers immunogenicity. It shares the same non-myelosuppressive toxicity profile — hypersensitivity, pancreatitis, thrombosis, hyperglycemia, and hepatotoxicity. If hypersensitivity develops, switch to an Erwinia-derived asparaginase to preserve asparagine depletion, which correlates with outcomes.

Related Therapies & Mechanisms

• Asparaginase (L-asparaginase, E. coli) (Elspar) — Other · ALL
• Obecabtagene autoleucel (Aucatzyl) — Other · ALL
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other