1. Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia
- Author
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Massimo Zucchetti, Arend von Stackelberg, Georg Hempel, Manfred Fobker, Martin Zimmermann, Christa E. Nath, Jana Golitsch, Martin Schrappe, Joachim Gerss, Carmelo Rizzari, Petr Smisek, Andishe Attarbaschi, Anja Möricke, Claudia Lanvers-Kaminsky, Alaeddin Khalil, Joachim Boos, Gudrun Würthwein, Valentino Conter, Nicola Gökbuget, Khalil, A, Wurthwein, G, Golitsch, J, Hempel, G, Fobker, M, Gerss, J, Moricke, A, Zimmermann, M, Smisek, P, Zucchetti, M, Nath, C, Attarbaschi, A, Von Stackelberg, A, Gokbuget, N, Rizzari, C, Conter, V, Schrappe, M, Boos, J, and Lanvers-Kaminsky, C
- Subjects
Adult ,medicine.medical_specialty ,Asparaginase ,Antineoplastic Agents ,Polyethylene glycol ,macromolecular substances ,Gastroenterology ,Antibodies ,Article ,Polyethylene Glycols ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Acute lymphocytic leukemia ,PEG ratio ,medicine ,Escherichia coli ,Humans ,Child ,Antibodies against polyethylene glycol ,biology ,business.industry ,Healthy subjects ,technology, industry, and agriculture ,Infant ,Hematology ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,Serum samples ,medicine.disease ,Concentration dependent ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Antibody ,business ,030215 immunology - Abstract
Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples from 701 children (673 with primary ALL, 28 with relapsed ALL) and 188 adults with primary ALL were analyzed for anti-PEG IgG and IgM. Measurements in 58 healthy infants served as a reference to define cut-points for antibody-positive and -negative samples. The prevalence of anti-PEG antibodies in ALL patients prior to the first administration of PEG-ASNase was 13.9% for anti-PEG IgG and 29.1% for anti-PEG IgM. After administration of PEG-ASNase the prevalence of anti-PEG antibodies decreased to 4.2% for anti-PEG IgG and to 4.5% for anti-PEG IgM. Pre-existing anti-PEG antibodies did not inhibit PEGASNase activity but significantly reduced PEG-ASNase activity levels in a concentration-dependent manner. Although pre-existing anti-PEG antibodies were not boosted, pre-existing anti-PEG IgG were significantly associated with first-exposure hypersensitivity reactions (Common Terminology Criteria for Adverse Events grade 2) (P
- Published
- 2020