Infusion Reactions With Monoclonal Antibody Therapy in Myeloma: Learning From Experience

The introduction of elotuzumab and daratumumab into clinical practice has dramatically improved the options for treating relapsed myeloma. These drugs are a new class of therapy that has been lacking in this hematologic malignancy: monoclonal antibody therapy directed at antigens on the myeloma cell surface. Both agents are effective in combination with the immunomodulatory agent lenalidomide in patients previously treated with one to three lines of therapy, and daratumumab has demonstrated efficacy in combination with bortezomib plus dexamethasone in a similar setting.1-3 Other key features include the important single-agent activity of daratumumab in highly advanced and refractory disease; elotuzumab, which lacks significant activity when given alone, has an interesting property of engaging natural killer cells as well as myeloma cells to bring them into proximity.1,4 As with any new cancer therapy, a learning curve exists in clinical practice to optimize drug administration. Although hematologists are comfortable with managing myelosuppression and GI toxicity, the primary toxicity consideration with these monoclonal antibodies is the infusion reactions, most commonly with the first infusion. Most of these reactions are mild, but particularly with the first dose of daratumumab, the risk of reactions involves the respiratory tract, with wheezing, shortness of breath, and other potentially serious symptoms. Therefore, optimal pre- and postinfusion medications become crucial, and details of the rate of infusion, suspension of the infusion to allow infusion reactions to resolve, and medications administered to speed the resolution of infusion reactions all become important to the treating health care team. The experience gained by centers that treat many patients may not be fully available in the drug product monograph, and articles such as the one accompanying this commentary by Nooka et al5 become highly relevant. In accordance with Nooka et al,5 we have found at Princess Margaret Cancer Centre that clinically significant infusion reactions are not frequent with elotuzumab; this feature, along with the relatively short infusion time, makes elotuzumab an attractive agent for patients of all ages and degrees of frailty. On the other hand, the potential for severe infusion reactions with the first dose of daratumumab mandate care in preparing the patient with adequate pre- and postmedications. We find that most reactions occur shortly after the second to third rate change (ie, when the rate is changed to 100 mL/h or 150 mL/h). Although we have not formally