Toxicities and side effects associated with intravenous infusions of murine monoclonal antibodies

Toxicity was assessed during and following 186 infusions of various murine monoclonal antibodies (MoAbs) in 82 patients afflicted with 10 different malignancies. Doses ranged from 0.5 to 500 mg per infusion and were administered over 0.25-24 h. Reactions of varying degrees were noted in 27 patients (33%) during or following 57 (31%) infusions. For antibodies that reacted with circulating cells, toxicity was seen in 20/82 of the first infusions compared with 0/55 for patients receiving antibodies that did not react with circulating cells. A 25% decrease in white blood cells (WBC) was associated with side effects in 40/66 courses whereas only 9/81 courses were associated with any sort of toxicity when the WBC decreased by less than 25%. Fevers, rigors, chills, and diaphoresis were observed in 21-23% of patients, but only in association with removal of circulating cells that bound the antibody. Presumed hypersensitivity reactions, including urticaria, pruritus, bronchospasm, and anaphylaxis occurred in 15 patients (18%). The two episodes of bronchospasm and single episode of anaphylaxis occurred in patients treated more than once, at least 2 weeks after a previous treatment. There was no clear relationship between dose or rate of infusion and toxicity for these antibodies. We conclude that murine MoAbs can be given with an acceptable frequency of serious allergic reactions and that the biologic effects of specific antibody-antigen reactions may be a more significant source of toxicity for such antibodies.