BCMA-Targeted Therapy in RRMM: Future Challenges and BiTE

Ola Landgren, MD, PhD:I would like to end the discussion here talking a little about the next step in research around theBCMA-targeted therapies in relapsed-refractory multiple myeloma. Where do you see the ongoing challenges being? If you look at the studies, if you look at the data on your own experience, where do you see the big hurdles?

Nina Shah, MD:The biggest hurdle I see for myeloma treatment in general is 1-and-done therapy. Meaning I don’t want to ever have to tell a myeloma patient, “You have to come back to me every month.” If we can figure out a way to get a durable response without having the patient come back forever, that would be a huge win. Some things may help us get there. For example, some of the patients with CAR [chimeric antigen receptor] T-cell mutation who had long-term outcomes—not all. Some, a few hand selected, have had those. If they have, we need to figure why they had it. We need the correlate of studies to understand and pick patients appropriately, maybe move those therapies forward in their treatment time, so that we’re not using exhausted T cells.

TheBCMAADC [antibody-drug conjugate] study actually treated people for 16 cycles. They did allow some people to stay on. But the point of that is that there were people who got limited cycles and still benefit, and I think that’s really important too. That’s going to be something ultimately the bispecifics will deal with. You know, are they going to be giving therapy forever or not?

We have to remember that these myeloma patients are coming to us, as you said, for 10 years, and we don’t want to make them come all the time. We love seeing them, but they don’t necessarily love seeing us every month. We want to make sure we make it something that may change their quality of life.

Ola Landgren, MD, PhD:To make sure we cover all the bases, we have talked about the DREAMM program for theBCMA-targeted ADCs. Are there any other drugs in development targeting BCMA that are ADCs?

Nina Shah, MD:I don’t know of any other drugs that are targetingBCMAfor ADC. There are the bispecifics we haven’t talked too much about, and we could talk a little about them. But for the bispecifics, we know that the only public data that have been available were the Amgen Inc 420, for 1 experience, and it was a continuous infusion of bispecific. Because of that, I think that it’s no longer being developed because it’s hard to do that. But it did show some preliminary efficacious results. I believe 7 of 10 people at their MTD [maximum tolerated dose] did have a response with some BR [bendamustine-rituximab]. It’s promising for sure, but I think we have to make it user friendly. As you said, people are on therapies for a long time, and they don’t want to be hooked up to an IV [intravenous] every day.

Ola Landgren, MD, PhD:I agree with you that the bispecific,BCMA-targeted therapies are very interesting. In preparation for today I looked a little into the presentations that are around the ASH American Society of Hematology 2019 Annual Meeting & Exposition. Looking online, I think Amgen 420—as you pointed out—seems to have been terminated, but they also in the public domain are developing this potentially for subcutaneous use. They had the 701 drug; that’s an infusional therapy.

And then Celgene Corp has also itsBCMACD3-targeted therapy that’s presented at the ASH 2019. In addition, Janssen Pharmaceutica has another drug, and Pfizer Inc has also a drug forBCMACD3. That may be additional; I did not read up on. But I think the message is that there are many of these bispecifics, but I think there’s only 1, as you point out,BCMA-targeted ADC drug.

Nina Shah, MD:Yeah, for now.

Transcript edited for clarity.