Toxicities associated with monoclonal antibody infusions in cancer patients.
The toxicity during and following 291 infusions of 19 murine and three human monoclonal antibodies (MoAB) in 177 cancer patients with 10 different malignancies was assessed. Doses ranged from 0.5 to 500 mg administered over 0.25 to 24 hours. Various reactions in varying degrees were observed in 45 (28%) patients during their first MoAb infusion. Nine additional patients experienced toxicity following a subsequent antibody infusion. Antibodies that reacted with circulating cells were associated with toxicity in 20 of 28 (71%) of the first infusions, compared to 24 of 127 (19%) for patients receiving antibodies that did not react with circulating cells. Fevers, rigors, chills, and diaphoresis were observed in 10% to 12% of the patients and were associated with binding to circulating cells. Presumed hypersensitivity reactions, including urticaria, pruritus, bronchospasm, and anaphylaxis occurred in 20 patients (11%). There were five episodes of bronchospasm and a single episode of anaphylaxis. Liver transaminases were elevated in 14%. There was no correlation between dose or infusion rate and toxicity. Murine monoclonal antibodies that are not conjugated to cytotoxic agents can be given with an acceptable frequency of side effects and serious allergic reactions. There is a small risk of anaphylaxis, and one should avoid rapid infusion of high antibody doses in the presence of circulating target cells and/or circulating free antigen.
Dillman
R O
RO
Experimental Clinical Oncology Section, Scripps Clinic and Research Foundation, La Jolla, CA 92037.
Beauregard
J C
JC
Jamieson
M
M
Amox
D
D
Halpern
S E
SE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology; D001666:Binding Sites, Antibody; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D006967:Hypersensitivity / Q000473:pathology; D007260:Infusion Pumps; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens