Asparaginase encapsulated in erythrocytes as second-line treatment in hypersensitive patients with acute lymphoblastic leukaemia
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Asparaginase is essential in treating acute lymphoblastic leukaemia (ALL). Asparaginase-related hypersensitivity causes treatment discontinuation, which is associated with decreased event-free survival. To continue asparaginase treatment after hypersensitivity, a formulation of asparaginase encapsulated in erythrocytes (eryaspase) was developed. In NOR-GRASPALL 2016 (NCT03267030) the safety and efficacy of eryaspase was evaluated in 55 patients (aged 1–45 years; median: 6.1 years) with non-high-risk ALL and hypersensitivity to asparaginase conjugated with polyethylene glycol (PEG-asparaginase). Eryaspase (150 u/kg) was scheduled to complete the intended course of asparaginase (1–7 doses) in two Nordic/Baltic treatment protocols. Forty-nine (96.1%) patients had asparaginase enzyme activity (AEA) ≥100 iu/l 14 ± 2 days after the first eryaspase infusion [median AEA 511 iu/l; interquartile range (IQR), 291–780], whereas six of nine (66.7%) patients had AEA ≥100 iu/l 14 ± 2 days after the fourth infusion (median AEA 932 iu/l; IQR, 496–163). The mean terminal half-life of eryaspase following the first infusion was 15.3 ± 15.5 days. Few asparaginase-related adverse events were reported; five patients (9.1%) developed clinical allergy associated with enzyme inactivation. Replacement therapy was successfully completed in 50 patients (90.9%). Eryaspase was well tolerated, and most patients had AEA levels above the therapeutic target after the first infusion. The half-life of eryaspase confirmed that a 2-week schedule is appropriate.
Originalsprog | Engelsk |
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Tidsskrift | British Journal of Haematology |
Vol/bind | 197 |
Udgave nummer | 6 |
Sider (fra-til) | 745-754 |
Antal sider | 10 |
ISSN | 0007-1048 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
Birgitte Klug Albertsen: sponsor for the investigator‐initiated study, the author has no financial conflict of interests. Speaker and/or advisory board honoraria from Erytech (2020) and Servier (2021). Kjeld Schmiegelow: speaker and/or advisory board honoraria from Illumina (2021), Jazz Pharmaceuticals (2020, 2021) and Servier (2020, 2021); speaker fee from Amgen (2020, 2021) and Medscape (2020, 2021); educational grant from Servier (2020, 2021); research grant from Novo Nordisk Foundation; speaker and/or advisory board honoraria from Illumina (2021), Jazz Pharmaceuticals (2020, 2021) and Servier (2020, 2021); speaker fee from Amgen (2020, 2021) and Medscape (2020, 2021); educational grant from Servier (2020, 2021); research grant from Novo Nordisk Foundation. Iman El Hariry: employed by Erytech. The remaining authors have no conflict of interest to declare.
Publisher Copyright:
© 2022 British Society for Haematology and John Wiley & Sons Ltd.
ID: 316675003