The Impact of CAR T-Cell Therapy on MM Treatment Paradigms

Noa Biran, MD, and David Siegel, MD, discuss how CAR T-cell availability has impacted the field of multiple myeloma.


Noa Biran, MD: How do you think these CAR [chimeric antigen receptor]T cells have impacted the field?

David Siegel, MD: It’s been a fascinating time. Sometimes you come across things that have an almost religious impact, that “Oh my God, how could this happen?” Patients who were clearly rapidly approaching death, but who are all of a sudden back to work, participating in the activities they’ve always participated in without even the encumberment of having to be constantly treated. Transplants sort of did that. You could transplant somebody and then watch them, and sometimes for very long periods of time. This is another such experience, except in a patient population that has been through almost everything we have to offer, and still can be brought back from the edge of the precipice and goes about life in a very fulfilling way. I think this is very gratifying.

Which of these agents is the best? To me, it almost doesn’t matter because it’s continuing to evolve. We have more things that are targeting BCMA [B-cell maturation antigen] in development all the time. The number of clinical trials out there is enormous, and we are going to have the opportunity to pick and choose which of these things looks the best. The short-term future targeting BCMA is very exciting. We’re lucky that we came across BCMA because, first of all, there is no such thing as a tumor-specific target, or very rarely are there such things. So you look for targets that are confined largely to the tumor cell and not to other cells. We in myeloma have this target, BCMA, which is expressed on other cells, but a very limited population of other cells. So we can attack it with really aggressive things, which if this target were shared widely, would be incredibly toxic. But we’ve got this really nice target that allows us to do those kinds of things. Just as an aside, myeloma has a whole series of those targets, and I hope we get to talk about some of that too.

Noa Biran, MD: That’s a great point. And even as good as this target is, we’re seeing patients relapse, right? Even those who achieve a CR [complete response] right away. And we’ve had some of these cases where we’re like, “Wow, it’s been 3 years, 4 years.” We even have some patients who were on the original trials who still are doing really well. But eventually, we know in the back of our heads that the disease is going to come back. So we have to look at these other targets.

In the context of the patient, we have to remember, what is the accessibility? Which patients do we choose for this type of therapy? As it stands now, it takes some time to both perform apheresis of the CAR T cells and to manufacture the CAR T cells. They are approved for patients who have failed 4 prior lines of therapy, and often these patients have rapidly progressing disease. And so once we are given a slot for apheresis of CAR T cells and we schedule the apheresis, we need to have a plan in that interim of what we’re going to do while the disease continues to progress, and that’s called bridging therapy.

Transcript edited for clarity.

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