Exploring CD38 Antibodies as Treatment in Multiple Myeloma

Thomas G. Martin, MD, clinical professor of Medicine and associate director of the Myeloma Program at University of California, San Francisco; and coleader of the Cancer Immunology & Immunotherapy Program at the Helen Diller Family Comprehensive Cancer Center, discusses the use of anti-CD38 antibodies in patients with multiple myeloma.

In multiple myeloma, anti-CD38 antibodies such as daratumumab (Darzalex) and isatuximab (Sarclisa) have been investigated for various settings including early relapse and relapsed/refractory disease. It has also been looked at as a combination therapy in frontline treatment. Martin believes this therapy should be used in the earliest possible setting for patients with multiple myeloma.

Transcription

0:08 | Literally over the last 10 years, we've had a lot of clinical trials that have focused on CD38 antibodies initially in the relapsed/refractory setting as single agents, then in early relapse as part of combination therapy, and now more recently as part of combination therapy for frontline treatment of patients with multiple myeloma. I think a couple of the most exciting recent data have been in the world of transplant-eligible and transplant-ineligible patients receiving quadruplets therapy with a CD38 antibody together with an IMiD [immunomodulatory imide drug], a proteasome inhibitor, and a steroid.

So these are therapies that are going to come to fruition and we're going to use quadruplet therapy as frontline-based therapy. It leaves the door open [to] what we're going to do after that, and there's some additional CD38s that are coming down the line.

What therapies are being looked at in clinical trials for multiple myeloma?

1:09 | The space that's going to open up is in the late-line relapsed/refractory space. We're going to need more agents because the CD38 antibodies that we currently have, daratumumab and isatuximab, are going to be used as frontline therapy in early relapse. The days where we saved something in the back pocket, a good drug in the back pocket so we had something down the road, are over in my mind. We try to use our best drugs up front as early as we can. So if we can use CD38 front line, we should do it. If not, we should use it in early relapse. When patients then progress, what are the next-generation antibodies that we can utilize in that circumstance?

We do have some next-generation CD38 antibodies. Some of these antibodies that are being tested are naked antibodies and perhaps bind better to cells that have high expression of CD38 on them. There's 1 that's been tested in clinical trial and we've seen some early data with TAK-079, which is a very interesting molecule. I'll talk about that and brush up on that at the review.

We also have some bispecific antibodies, some that actually bind to CD38 and CD3. They've had difficulty in development with some bone marrow toxicity associated with them. But we also have some CD38s in development that are attached to poisons. So these are actually, again, very interesting next-generation molecules that might make binding to CD38 with 1 of these antibodies more potent, especially in patients that have previously been treated with CD38 antibodies. Then we have a whole host of bispecific T-cell engager antibodies that are important antibodies for the future also and can be used in I think the CD38 refractory space.