CAR T-cell Therapy and Bispecific Monoclonal Antibodies Come with Potential Side Effects

This week's "Ask Dr. Durie" comes from a patient who has heard about all of the exciting new immune therapies, particularly the bispecific monoclonal antibodies and CAR T-cell therapies. The engineered T cells which are used to attack the myeloma. But her particular question is: this is great, but what about the side effects of these treatments? The access to these treatments? The difficulties in managing the ongoing issues with care when you take these wonderful new therapies?

And so the first thing to say is that this is, in fact, a very important question. These are great new therapies. But, for example, CAR T-cell therapy requires the T cells to be harvested from the patient and then sent off for manufacturing to be engineered so that the T cells will, in fact, attack the patient's myeloma.

While that is happening, the patient needs to take what is called bridging therapy. And then once the cells are grown up and ready for administration, they come back to the hospital a month or so later. And so there's a lot of time involved. There are only a certain number of centers capable of doing this. And so there are access issues.

There are a lot of logistic concerns. And then, this is a difficult treatment to go through. The big, big advantage is that it is what is called "one and done" in the sense that once those T cells come back and are administered, then the patient can have a really dramatic benefit on response to therapy and then will be off therapies.

So this is a big, big advantage. But access to this has been a particular problem over these last two and three years. Then the bispecific obviously are what are called "off the shelf". So this means that they are much more readily available and teclistamab is approved—a BCMA targeted bispecific. But the concern is that with ongoing therapy, there is a significant risk of suppression of the normal immune system and a risk of pneumonia, which can be quite serious, as well as other kinds of infection.

And linked to that, fatigue, reduced blood sugars, blood counts, and the like. And so, not a trivial type of therapy. And so the question is, yes, these are therapies that are great. But are there other options?

And so, the answer to that is yes. And so the important advice is to listen very carefully to all of the details of the therapies, which might be available in your case, but also look at information about more standard approaches that are standard approaches for use in early disease.

For example, Daratumumab combined with Pomalidomide and dex (DPd) is a very well-tolerated regimen which can be very effective in the relapse setting. Even simpler recombinant combinations can be used in the relapse setting. And so the strong advice I give to patients is to look at all of these things carefully.

This is a time to definitely consider a second opinion, whether that be live or through a Zoom in some fashion. But talk to your doctor about that and get all of the input that you need to look at. Yes, the tremendous benefits of these new immune therapies. But what is the access? What are the implications for quality of life?

What could be the costs to you and your family? And so, the BOTTOM LINE, a very good question, very, very important phase of the disease in the relapsed setting, too, to look at all the options and see what are the true pros and cons of these exciting new immune therapies for.