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Acute Lymphoblastic Leukemia
Pre-existing antibodies against polyethylene glycol reduce asparaginase activities
on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia
Alaeddin Khalil,1 Gudrun Würthwein,1 Jana Golitsch,1 Georg Hempel,2 Manfred Fobker,3 Joachim Gerss,4 Anja Möricke,5 Martin Zimmermann,6 Petr Smisek,7 Massimo Zucchetti,8 Christa Nath,9 Andishe Attarbaschi,10 Arend von Stackelberg,11 Nicola Gökbuget,12 Carmelo Rizzari,13 Valentino Conter,13 Martin Schrappe,5 Joachim Boos1 and Claudia Lanvers-Kaminsky1
1Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany; 2Department of Pharmaceutical and Medical Chemistry, Clinical Pharmacy, University of Münster, Münster, Germany; 3Center of Laboratory Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, Germany; 4Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany; 5Department of Pediatrics, University Medical Center Schleswig- Holstein, Campus Kiel, Kiel, Germany: 6Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany; 7Department of Pediatric Hematology and Oncology, University Hospital Motol, Praha, Czech Republic; 8Laboratory of Cancer Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; 9Departments of Biochemistry and Oncology, The Children’s Hospital at Westmead, Sydney Pharmacy School, University of Sydney, Sydney, Australia; 10Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria; 11Departments of Pediatric Oncology/Hematology and of General Pediatrics, Charité -University Medicine Berlin, Berlin, Germany; 12Department of Medicine, University Hospital, Frankfurt am Main, Germany and 13Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano- Bicocca, MBBM Foundation, ASST-Monza, Monza, Italy
ABSTRACT
Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluat- ed 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 PEG- ASNase 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 signifi- cantly associated with first-exposure hypersensitivity reactions (Common Terminology Criteria for Adverse Events grade 2) (P<0.01; Fisher exact test). Two of four 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 activity (≥100 U/L). In conclusion, pre-existing anti-PEG antibodies were detect- ed in a considerable proportion of patients with ALL and although they did not inhibit PEG-ASNase activity, they were associated with lower
Ferrata Storti Foundation
Haematologica 2022 Volume 107(1):49-57
Correspondence:
CLAUDIA LANVERS-KAMINSKY
lanvers@uni-muenster.de
Received: May 19, 2020.
Accepted: November 25, 2020. Pre-published: December10,2020.
https://doi.org/10.3324/haematol.2020.258525 ©2022 Ferrata Storti Foundation
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