BCMA-Targeted Therapy for Relapsed/Refractory Multiple Myeloma - Episode 7

What's Next for BCMA-Targeted ADCs and CAR-T Therapy in RRMM?

December 10, 2019

Ola Landgren, MD, PhD:What additional research would you like to see when it comes to the antibody-drug conjugate [ADC],BCMA-targeted drug that we’re talking about? Is there anything we have not covered?

Nina Shah, MD:That drug, as we talked about, we know that it has efficacy, so we really need to make it usable. I’d love to see more research on different dosing options that patients could have so that the patient, so that the doctors who are prescribing this—including me and you—have a really good guideline about maybe dose reducing. If we still have the same efficacy, maybe have more or less frequent dosing. Stopping and starting as you mentioned and what that means for efficacy. I’d just like to have a little more information and maybe plan clinical trials around difficult dosing, dose modifications, to help us understand if they’re still efficacious.

Ola Landgren, MD, PhD:I agree with that. How about if you think of maybe fewer or lower doses or something in combination? What about combination therapies? Is there something you would like to see?

Nina Shah, MD:Yeah. Of course myeloma is the alphabet soup. You know, we put all these letters together to make combinations. And 1 of the great things about the immunotherapies, including the ADCs, the bispecifics, and the CAR T, is that they lend themselves to combining with drugs that we already have. For example, the IMiDs [immunomodulatory imide drugs], because we have a way to stimulate the immune system and work better. There may be even a new role for PD-1 [programmed cell death protein 1] inhibitor; we don’t even know. But for the drugs that we do have FDA approved, that we could more easily slot in to compare, the next step will be, for example, ADC combination with IMID. I think that would be very user friendly for outpatients, and there would be a rationale for it.

Ola Landgren, MD, PhD:Given that we sit here talking about ADC, targetingBCMA, we mentioned all these different bispecific antibodies, and I also know, you have been leading, are leading 1 of the CAR T cells in parallel in your program. Where do you see the CAR T cells going in competition with all these other antibodies?

Nina Shah, MD:Yeah, that’s a really hard question, because first of all it’s going to be referral-pattern based, right? Because not every patient is going to come to a center for CAR T cells. But let’s say they had referrals, they could choose whatever they wanted. Let’s say it was very free. In that situation, as I see it now, maybe the patients would come to CAR T first, and I say that because there’s likely to be an FDA approval soon. After that, if there was CAR T failure, there’s still a role for bispecifics orBCMAADC, which at that time they could potentially get in the community.

While they’re a little younger and a little less pretreated in that sense, maybe they can go for something that’s more intense as far as logistics and coming to a center, but afterward could maybe also be rescued with aBCMABiTE [bispecific T-cell engager] or ADC. But I can’t predict the future necessarily. That’s just how I see it right now.

Ola Landgren, MD, PhD:You give a very good overview there, and if I just add 1 little detail, I think in the end of 2019 the first allogeneic CAR T cell is also coming.

Nina Shah, MD:Yeah.

Ola Landgren, MD, PhD:Here you have an on-the-shelf product that is still cell based. We don’t know; this is very early obviously.

Nina Shah, MD:I actually am really excited about the allogeneic products, because I think this idea of off-the-shelf is a big one. You know when you take people to CAR T therapy you have to wait that 5 weeks, and there are a lot of logistics. But if you could perhaps grab some pills off a shelf and give them and they worked, that would be great. Of course there are going to be issues with rejection by host immune system and issues with persistence, and these are just the things that have to be overcome. But thankfully the science is moving faster. As you know, it already has. Then we are in clinical trials. I’m hoping we’ll get an answer to that sooner rather than later.

Ola Landgren, MD, PhD:In our lab, and I’m sure in your lab as well and in other labs, there’s work ongoing with the CAR-N case that also can be done on the shelf.

Nina Shah, MD:Yup.

Ola Landgren, MD, PhD:That has not yet been in humans.

Nina Shah, MD:Right.

Ola Landgren, MD, PhD:That would be another opportunity for on-the-shelf with cell-based therapy.

Nina Shah, MD:Yes, it will. And those really don’t tend to cause graft-vs-host disease at all, so that’s a really good option as well.

Ola Landgren, MD, PhD:I’d like to thank you so much, Nina, for this very insightful discussion. And I would like to thank our audience for watching thisTargetedOncology™ presentation on precision medicine. Thank you very much.

Transcript edited for clarity.