Hypersensitivity to Pegylated E.coli asparaginase as first-line treatment in contemporary paediatric acute lymphoblastic leukaemia protocols: a meta-analysis of the Ponte di Legno Toxicity working group

Eur J Cancer. 2022 Feb:162:65-75. doi: 10.1016/j.ejca.2021.11.016. Epub 2021 Dec 23.

Abstract

Background: Hypersensitivity reactions to asparaginase challenge its use and occur frequently (30-75%) after native Escherichia Coli (E.coli) asparaginase. Comparison of incidence of allergic reactions to pegylated E.coli asparaginase (PEGasparaginase) across contemporary paediatric acute lymphoblastic leukaemia (ALL) protocols is lacking.

Method and patients: Questionnaires were sent to all members of the international ALL Ponte di Legno Toxicity Working Group. Meta-analyses were conducted to estimate the incidence of three types of hypersensitivity (allergy, allergic-like reaction and silent inactivation). Information on protocol level regarding PEGasparaginase dosing regimen, administration route and use of therapeutic drug monitoring was collected for risk analysis.

Results: Newly diagnosed patients with ALL (n = 5880), aged 1-24 years old, were enrolled in seven different upfront ALL protocols using PEGasparaginase as first-line treatment. The incidence of allergic reactions (sum of allergies and allergic-like reactions) [95% confidence interval] was 2% [1%; 3%] during induction and 8% [5%; 11%] during postinduction. Route of administration, number of doses, dosage and number of PEGasparaginase-free weeks did not significantly influence risk of hypersensitivity. Multivariate meta-regression analysis suggests that initiation of PEGasparaginase in postinduction and higher number of PEGasparaginase-free intervals increased the risk for allergic reactions. 9-16% and 23-29% of all hypersensitivities were allergic-like reactions and silent inactivation, respectively.

Conclusion: The incidence of allergic reactions is lower in protocols using PEGasparaginase as first-line treatment compared with that reported for E.coli asparaginase or PEGasparaginase after E.coli asparaginase. Postinduction phase, a higher number of PEGasparaginase-free intervals, and initiation of PEGasparaginase in postinduction phase are risk factors for allergic reactions. These results are important for planning of PEGasparaginase administrations in future frontline therapy.

Keywords: Acute lymphoblastic leukaemia; Hypersensitivity; PEGasparaginase; Paediatric ALL; Risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents* / therapeutic use
  • Asparaginase / adverse effects
  • Child
  • Child, Preschool
  • Drug Hypersensitivity* / epidemiology
  • Drug Hypersensitivity* / etiology
  • Humans
  • Hypersensitivity* / complications
  • Hypersensitivity* / drug therapy
  • Infant
  • Meta-Analysis as Topic
  • Polyethylene Glycols
  • Pons
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Young Adult

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • Asparaginase