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

: Lynggaard Line S, Vaitkeviciene Goda, Langenskiold Cecilia, Lehmann Anne K, Lähteenmäki Päivi M, Lepik Kristi, El Hariry Iman, Schmiegelow Kjelt, Albertsen Birgitte K

Publisher: WILEY

: 2022

: British Journal of Haematology

: BRITISH JOURNAL OF HAEMATOLOGY

: BRIT J HAEMATOL

: 197

: 6

: 745

: 754

: 10

: 0007-1048

: 1365-2141

DOI: https://doi.org/10.1111/bjh.18152(external)

: https://doi.org/10.1111/bjh.18152(external)

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.