Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials

Leuk Lymphoma. 2018 Jul;59(7):1624-1633. doi: 10.1080/10428194.2017.1397658. Epub 2017 Nov 8.

Abstract

PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection.

Keywords: ALL; Pegaspargase; asparaginase; hypersensitivity; intramuscular; intravenous.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Age Factors
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Asparaginase / administration & dosage
  • Asparaginase / adverse effects*
  • Asparaginase / therapeutic use
  • Biomarkers
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / epidemiology*
  • Drug Hypersensitivity / etiology*
  • Female
  • Humans
  • Incidence
  • Infusions, Intravenous
  • Injections, Intramuscular
  • Leukemia / complications
  • Leukemia / drug therapy
  • Male
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / adverse effects*
  • Polyethylene Glycols / therapeutic use
  • Public Health Surveillance
  • Severity of Illness Index

Substances

  • Antineoplastic Agents
  • Biomarkers
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase