Efficacy and safety of recombinant E. coli asparaginase in children with previously untreated acute lymphoblastic leukemia: A randomized multicenter study of the Dutch Childhood Oncology Group. Issue 8 (4th May 2018)

• Record Type: Journal Article
• Authors: van der Sluis, Inge M.; de Groot‐Kruseman, Hester; te Loo, Maroeska; Tissing, Wim J.E.; van den Bos, Cor; Kaspers, Gertjan J.L.; Bierings, Marc; Kollen, Wouter J.W.; König, Thorsten; Pichlmeier, Uwe; Kühnel, Hans‐Jürgen; Pieters, Rob
• Is Part Of: Pediatric blood & cancer. Volume 65:Issue 8(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-05-04
• Subjects: efficacy -- pediatric acute lymphoblastic leukemia -- randomized trial -- recombinant asparaginase -- toxicity; Tumors in children -- Periodicals; Blood -- Diseases -- Periodicals; Cancer in children -- Periodicals; 618.92
• DOI: 10.1002/pbc.27083
• Languages: English
• ISSNs: 1545-5009

Abstract

Abstract: Background: The efficacy and safety of recombinant Escherichia coli –asparaginase (rASNase) was compared to native E.coli asparaginase (Asparaginase medac). Methods: One hundred and ninety‐nine children with newly diagnosed acute lymphoblastic leukemia were randomized to receive one of both agents at a dose of 5, 000 U/m² during induction (eight doses) and 10, 000 U/m² during the postinduction phase (only high‐risk patients; standard‐ and medium‐risk patients received pegaspargase). Results: Median trough serum asparaginase activity levels were comparable between both groups; they ranged from 143 to 182 U/l during induction and were above the target value of 100 U/l. Complete asparagine depletion in serum was achieved in 97.9% of patients, with no significant differences between both groups. On day 33 (end of induction), only two (2%) evaluable patients in each group had measurable asparagine serum levels, and complete asparagine depletion in the cerebrospinal fluid was achieved in 98.8% and 93.6% of the patients with rASNase and Asparaginase medac, respectively. During induction, 2.1% and 5% of patients developed an allergic reaction to rASNase or Asparaginase medac, respectively. Approximately 41% of the patients in both groups had a clinical allergy or enzyme inactivation to the first dose of any asparaginase preparation in postinduction. A comparable proportion of patients in both groups developed anti‐asparaginase antibodies (57%) during repeated administration of asparaginase. Minimal residual disease levels at the end of induction, 5‐year event‐free survival, and 5‐year cumulative incidence of relapse did not differ between both groups. Conclusion: The efficacy, safety, and immunogenicity of both asparaginase preparations are comparable. This trial was registered atwww.clinicaltrials.gov as #NCT00784017; EudraCT number 2006‐003180‐31.