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Complications of monoclonal antibody therapy.

iNfusioN reaCTioNs An infusion reaction may range from mild to lethal. The severity is given a rating on a scale of one (mild) to five (lethal). Most often the signs and symptoms are mild (grade one or two). Common signs and symptoms include fever, flushing, rigors, chest discomfort, abdominal pain, nausea, vomiting, diarrhea, and rashes. Rarely, MCAs can cause anaphlaxis. It may be initially difficult to distinguish a mild reaction from anaphylaxis. However, the presence of respiratory changes and urticaria are more specific to anaphylaxis and in contrast, myalgias are more likely to accompany a mild reaction. A generalized symptomatic response to infusion of MCAs typically occurs within the first two hours, but may be delayed up to 14 days after treatment. The highest risk of a reaction is during the first or second exposure to the MCA. The risk declines with repeated exposure, but 10-30% of reactions occur beyond the first two doses. MCAs most associated with early infusion reactions are infliximab, rituximab, gemtuzumab, alemtuzumab, trastuzumab, cetuximab, ofatumumab. Prevention of mild infusion reactions with premedication is routine; however, anaphylaxis may still occur. Commonly prescribed premedication regimens are diphenhydramine and acetaminophen. A patient with a mild reaction should temporarily stop the infusion, and receive symptom relief using an IV antihistamine with oral acetaminophen. They may be re-challenged at a reduced infusion rate (50%) after symptoms have resolved. If a patient develops repeated mild reactions then a referral to an allergy specialist for a desensitization protocol may be considered. A patient with a severe response consistent with anaphylaxis should not be re-challenged. Initial management of suspected anaphylaxis is to stop the infusion. Then intramuscular injection of epinephrine should be given while support is called. If there is no pulmonary contraindication the patient is placed in a supine position, given supplemental oxygen, and a safe airway should be maintained. Volume resuscitation, intravenous antihistamines, and bronchodilators may be administered.