Transcript:Shaji Kumar, MD: Using monoclonal antibodies for treatment of hematological malignancies is not anything new for practitioners. Rituximab has been used for treatment of lymphoma for almost two decades now. So, many of the hematologists and oncologists are very familiar with the use of monoclonal antibodies, but clearly this is a new paradigm for treatment for multiple myeloma patients. The key things that need to be kept in mind are the toxicities that are fairly specific and unique to monoclonal antibodies, and among them, infusion reactions are right on top of the list. Making sure the patients are well pre-medicated to avoid the allergic reactions or the infusion reactions is critical to management of these patients. The fact that these infusion reactions can occur very commonly with these monoclonal antibodies—more so with daratumumab than with elotuzumab—is something that the patients, as well as the physicians and the nursing staff, should be aware of.
There are several different ways and approaches to decrease the risk of developing infusion reactions. Obviously, the pre-medication is a critical part. That should include the use of some of the steroid medications. Sometimes, giving the steroid medications ahead of time can also help with decreasing the risk of infusion reactions. The other thing to keep in mind is that most of those infusion reactions tend to happen with the very first infusion, and the proportion of patients actually getting infusion reactions after the first infusion is pretty small. In fact, with daratumumab, the first infusion, there’s a 50% chance of developing an infusion reaction of any grade. But with second and third infusion, it’s only 6% and 4%. With elotuzumab, it’s about a 10% risk of infusion reactions, but, again, with the subsequent cycles, it’s extremely small.
The specific things that we need to watch out for are the difficulty with breathing, which many of these patients can have, and drop in the blood pressure. This can all be managed by slowing down the infusion or stopping the infusion, and then restarting the infusion very slowly, and then accelerating the infusion rate very slowly with the first infusion.
Patients can also benefit from use of additional steroid medications, as well as other medications like Benadryl and H2 blockers. If patients are having difficulty with breathing, sometimes inhaled bronchodilators can be of benefit, as well, in this group of patients. It’s also important to plan ahead because patients may have to stay in the infusion center for up to 8 hours for the first infusion. Subsequent infusions can be given much more acutely, and that certainly facilitates ongoing therapy in these patients. The other side effects that we need to watch out for include changes in the blood counts, so these patients should have weekly blood counts prior to therapy—at least in the beginning. But once the patients are tolerating the drugs well, these tests can be spaced out much more.
In addition to the infusion reactions and other toxicities that you see in patients getting monoclonal antibodies, there are a couple of things that need to be highlighted. One of them is the effect of daratumumab on the ability to type and crossmatch if someone needs red blood cell transfusion. Now, the daratumumab monoclonal antibody can also bind to the red blood cells, and that makes it difficult for the blood banks to actually find a good match for red blood cell transfusion if someone were to need it. And, often, myeloma patients can be anemic and might need that. So, it’s important to make sure every patient is typed and their blood group determined, and they are screened for antibodies before they get started on daratumumab. Once these patients are on therapy with daratumumab and they need a red blood cell transfusion, it’s very important that the blood bank be informed ahead of time that this patient is on therapy, so that they can do specific assays to prevent that indifference that can often happen with the monoclonal antibody.
Now, one of the other things we do see with these monoclonal antibodies is a decrease in the number of lymphocytes. And that might predispose patients to some of these infections, especially some of the wild infections like reactivation of Herpes zoster or development of shingles. Now, many of these patients, since they have cancer, are not necessarily eligible to get the vaccination, and we’re not even sure it might work well in these patients. So, most of these patients should be on a prophylactic treatment, like Acyclovir, while they are getting these therapies. And we have been using it for a long time in patients getting proteasome inhibitors, and I think the same principle applies for patients getting these drugs and the various combinations.
Transcript Edited for Clarity