TY - JOUR AU - Khalil, Alaeddin AU - Würthwein, Gudrun AU - Golitsch, Jana AU - Hempel, Georg AU - Fobker, Manfred AU - Gerss, Joachim AU - Möricke, Anja AU - Zimmermann, Martin AU - Smisek, Petr AU - Zucchetti, Massimo AU - Nath, Christa AU - Attarbaschi, Andishe AU - von Stackelberg, Arend AU - Gökbuget, Nicola AU - Rizzari, Carmelo AU - Conter, Valentino AU - Schrappe, Martin AU - Boos, Joachim AU - Lanvers-Kaminsky, Claudia PY - 2022/01/01 Y2 - 2024/03/28 TI - Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated <i>E. coli</i> asparaginase in children with acute lymphocytic leukemia JF - Haematologica JA - haematol VL - 107 IS - 1 SE - Articles DO - 10.3324/haematol.2020.258525 UR - https://haematologica.org/article/view/haematol.2020.258525 SP - 49-57 AB - 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 of 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 reference to define cut-points for antibody-positive and -negative samples. Anti-PEG antibodies were detected in ALL patients prior the first PEG-ASNase with a prevalence of 13.9% (anti-PEG IgG) and 29.1% (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 PEG-ASNase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner. Although pre-existing anti-PEG antibodies did not boost, pre-existing anti-PEG IgG were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2) (p<0.01; Fisher’s exact test). Two of 4 patients with pre-existing anti-PEG IgG and first-exposure hypersensitivity reactions were not switched to Erwinia ASNase and continued on PEG-ASNase with sufficient activities (≥100U/L).Pre-existing anti-PEG antibodies were detected in a considerable proportion of patients with ALL, did not inhibit PEG-ASNase activity but were associated with lower serum PEGASNase activity levels. Patients with pre-existing antibodies may show mild to moderate signs of hypersensitivity reaction after their first PEG-ASNase, which may be successfully addressed by re-challenge. ER -