Asparaginase encapsulated in erythrocytes as second-line treatment in hypersensitive patients with acute lymphoblastic leukaemia.

Autor: Lynggaard LS; Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Vaitkeviciene G; Center of Pediatric Oncology and Hematology, Vilnius University Hospital Santaros Klinikos and Vilnius University, Vilnius, Lithuania., Langenskiöld C; Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden., Lehmann AK; Department of Hematology, Haukeland Universitetssjukehus, Bergen, Norway., Lähteenmäki PM; Department of Pediatric and Adolescent Medicine, Turku University Hospital, Turku, Finland., Lepik K; Department of Hematology and Oncology, Tallinn Children's Hospital, Tallinn, Estonia., El Hariry I; Erytech, Cambridge, Massachusetts, USA., Schmiegelow K; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.; Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark., Albertsen BK; Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2022 Jun; Vol. 197 (6), pp. 745-754. Date of Electronic Publication: 2022 Mar 28.
DOI: 10.1111/bjh.18152
Abstrakt: 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.
(© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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