Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patients

• Published in: Cancer Vol. 110; no. 1; pp. 103 - 111
• Main Authors: Armstrong, Jonathan K., Hempel, Georg, Koling, Susanne, Chan, Linda S., Fisher, Timothy, Meiselman, Herbert J., Garratty, George
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2007; Wiley-Liss
• Subjects: acute lymphoblastic leukemia; Agglutination Tests - methods; Antibodies - blood; antibody; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Asparaginase - immunology; Asparaginase - pharmacokinetics; Asparaginase - therapeutic use; asparaginase medac; Biological and medical sciences; Child; Female; Flow Cytometry - methods; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Metabolic Clearance Rate; Oncaspar; PEG‐asparaginase; poly(ethylene glycol); Polyethylene Glycols - pharmacokinetics; Polyethylene Glycols - therapeutic use; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Reproducibility of Results; Treatment Outcome; Tumors; Antineoplastic agent; Human; Enzyme; Antibody; Acute leukemia; Malignant hemopathy; Lymphoid neoplasm; Oncaspar; Ethylene oxide polymer; Cancerology; Treatment; PEG-asparaginase; poly(ethylene glycol); acute lymphoblastic leukemia; Lymphoproliferative syndrome; Hydrolases; asparaginase medac; Acute lymphocytic leukemia; Asparaginase
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22739

BACKGROUND. Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti‐PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti‐PEG was associated with rapid clearance PEG‐ASNase. METHODS. The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin‐Frankfurt‐Muenster 2000 studies. Twenty‐eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG‐ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti‐PEG using 2 techniques: 1) serology, by agglutination of PEG‐coated red blood cells; 2) flow cytometry, by analysis of 10 μm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG‐ASNase‐treated patients with undetectable ASNase activity, anti‐PEG was detected in 9 by serology and in 12 by flow cytometry. Anti‐PEG was detected in 1 PEG‐ASNase‐treated patient with lower ASNase activity (123 U/L). No relation was observed between anti‐PEG and serum ASNase activity for patients treated with unmodified ASNase. CONCLUSIONS. The presence of anti‐PEG was very closely associated with rapid clearance of PEG‐ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti‐PEG on PEG‐conjugated agents. Screening and monitoring for anti‐PEG may allow identification of patients for whom a modified dosing strategy or use of a non‐PEGylated drug would be appropriate. Cancer 2007. © 2007 American Cancer Society. Rapid clearance of poly(ethylene glycol)‐asparaginase (PEG‐ASNase) has been reported for up to one‐third of patients treated for acute lymphoblastic leukemia. The presence of antibody specific to poly(ethylene glycol) was very closely associated with undetectable serum ASNase activity in PEG‐ASNase‐treated patients.