Keith Stewart, MB ChB: Monoclonal antibodies are transforming the way we treat multiple myeloma as new agents that we can combine with many other drugs safely and effectively with very impressive results. There are now 2 monoclonal antibodies approved for use: elotuzumab, which targets the cell surface marker SLAMF7, and daratumumab, which targets the cell surface marker CD38. Both have been shown in phase III clinical tests to combine very well with proteasome inhibitors and with immune modulator drugs, such as lenalidomide or even pomalidomide. Our experience, clinically, has been very positive for both agents. Elotuzumab is perhaps a drug better suited for a slower progressing disease, perhaps patients who are more elderly, because of the frequency and duration of infusions in the side effect profile. Daratumumab is proving to be a highly effective drug across the spectrum of treatments from first relapse through endstage disease. It is a drug that is quite safe to give and can combine easily, and probably has some of the best reported results yet in multiple myeloma in the relapsed setting.
As with most monoclonal antibodies, infusion reactions can occur. Particularly notable perhaps with the drug daratumumab are some upper respiratory tract side effects including wheezing, running nose, and running eyes that do require some attention. For both monoclonal antibodies that we use, daratumumab and elotuzumab, premedication is recommended. This is usually a combination, as described in the package insert, of a corticosteroid, either Solu-Medrol or dexamethasone, with an H1/H2 blocker such as Benadryl (diphenhydramine) or cetirizine (Zyrtec), as examples. And, sometimes, acetaminophen (Tylenol) is also added to that combination.
Today, both these monoclonal antibodies are given intravenously. Daratumumab, particularly during the first infusion, can take most of the day. It can take anywhere from 6 to 8 hours to deliver sometimes because it needs to be started slowly and the dose slowly titrated upwards. Elotuzumab can be given over a shorter period of time. It’s given every 2 weeks instead of every week.
After the first infusion of either drug with subsequent infusions, particularly with daratumumab, the infusion time will generally become shorter as long as the patient has not experienced toxicities or infusion-related reactions. It’s important to know that most of the reactions with daratumumab, as an example, occur within the first infusion in up to 40% of patients. But, generally, it did not recur with subsequent infusions. So, it’s really the first infusion that is slower.
Practical recommendations for the infusion, which can take the entire day, are to bring the patient in early in the morning and get started early, so they can finish before the unit closes in the evening. This is obviously reasonable if your infusion unit is open for long enough. In some instances, patients have had to be admitted overnight to a hospital if the infusion unit closes early. But, generally speaking, we found that we can get the infusion, particularly the first week, within a working day if the patient starts early.