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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | European Journal of Cancer |
| Vol/bind | 162 |
| Sider (fra-til) | 65-75 |
| Antal sider | 11 |
| ISSN | 0959-8049 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Leiah J Brigitha: none. Marta Fiocco: none. Rob Pieters received research support and consultancy fees from Jazz Pharmaceuticals and Servier. Birgitte K Albertsen is sponsor of the investigator-initiated trial NOR-GRASPALL2016 supported by Erytech and was speaker and/or Advisory Board Honoraria from Erytech (2021) and Servier (2021). Gabriele Escherich: none. Elixabet Lopez-Lopez: none. Veerle Mondelaers acknowledges support from the Cancer Plan Action 29 from the Belgian Federal Public Service of Health, the Flemisch League Against Cancer and vzw. Kinderkankerfonds. Ajay Vora acknowledges Bloodwise funding for UKALL 2011. Lynda Vrooman: none. Kjeld Schmiegelow was speaker and/or Advisory Board Honoraria from Jazz Pharmaceuticals (2020, 2021) and Servier (2020), and received a speaker fee from Amgen (2020) and Medscape (2020, 2021), and Educational grant from Servier (2020, 2021). All the services relate to the use of asparaginase and/or treatment of acute lymphoblastic leukemia. Inge M van der Sluis received research support and consultancy fees from Jazz Pharmaceuticals and Servier.
Funding Information:
BSPHO: none. CoALL: none. DCOG: none. DFCI: none. NOPHO: The authors BKA and KS would like to thank the Danish Cancer Society and the Danish Childhood Cancer Society for supporting this study. LAL/SEHOP-PETHEMA: Author ELL would like to thank all involved hospitals for data collection. UKALL: Author AV would like to thank Amy Kirkwood, UKALL 2011 statistician, for collecting the UK data.
Publisher Copyright:
© 2021 The Author(s)