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Rigshospitalet - a part of Copenhagen University Hospital
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Asparaginase encapsulated in erythrocytes as second-line treatment in hypersensitive patients with acute lymphoblastic leukaemia

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  • Line Stensig Lynggaard
  • Goda Vaitkeviciene
  • Cecilia Langenskiöld
  • Anne Kristine Lehmann
  • Päivi M Lähteenmäki
  • Kristi Lepik
  • Iman El Hariry
  • Kjeld Schmiegelow
  • Birgitte Klug Albertsen
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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.

Original languageEnglish
JournalBritish Journal of Haematology
Volume197
Issue number6
Pages (from-to)745-754
Number of pages10
ISSN0007-1048
DOIs
Publication statusPublished - Jun 2022

Bibliographical note

© 2022 British Society for Haematology and John Wiley & Sons Ltd.

    Research areas

  • acute lymphoblastic leukaemia, asparaginase, asparaginase encapsulated in erythrocytes, hypersensitivity

ID: 78117574