iwMyeloma 2024 | Session highlights: sequencing CAR-T cells & bispecifics and managing toxicities

Hello, my name is Gareth Morgan, and I’m professor of hematology at New York University’s Langone Health Center in New York City. I’m here today with my two colleagues.

Hi, I’m Faith Davies, and I’m also a professor of hematology in New York City.

And I’m Lou Williams, I’m an associate staff member in the plasma cell group at the Cleveland Clinic in Cleveland.

So, it was a great session today at the iwMyeloma. Perhaps you could just tell me what were some of the exciting things for you?

Okay, so I’m going to take a few bits from people’s talks. So, in the session today, it was about CAR-T, bispecifics, and antibody-drug conjugates. And so, I particularly enjoyed putting the data together about GPRC5D, because obviously we have the talquetamab results, but then there’s also some new CAR-T’s coming through, using the same target. And then there’s also some ADCs coming through using the same target. And so, I thought it was just interesting thinking about, how we can use that drug, how we can sequence it with BCMA’s. And then also a little bit more about some of the, I’m going to say, on target but off tumor effects, if that’s the right expression, you know, the problems with the nails and the skin and so on. So I enjoyed just like hearing an update about where that’s moving to.

Great.

Lou?
I particularly enjoyed a couple of aspects of today’s talks. I enjoyed, gaining a little bit more of an understanding of the potential roles for soluble BCMA and how that may or may not impact the efficacy of bispecifics. And I also enjoyed the talks surrounding the use of CAR-T in elderly patients, and the potential to extend the benefit of this therapy to patient populations that we don’t necessarily see included in clinical trials.

So I thought, you know, on the kind of negative side, I guess, was we understand now much better how these anti-BCMA and GPRC5D agents work, that if you press on the target, you’re going to lose the target and get resistance. But the optimistic thing I thought was, that using combinations of these drugs, I think we should be able to overcome that. And actually, what we worried about for a long time, this exhaustion, is not such a relevant thing clinically if we take appropriate strategies like, shorter durations of treatment, longer time between the drugs.  So, what do you guys think about that?

I find that the idea of alternating targets, especially using the bispecific therapies, to be an interesting approach. I think overall, what stands out to me is that there is a lot of, you know, there’s a lot of thought and effort being invested in planning studies that will, you know, attempt to address exhaustion, will attempt to take a planned and strategic approach to these issues in the future. And I think if we can translate that kind of thinking to the clinic, I don’t know that we know the answer yet, but we’ll be able to use, you know, to sort of actualize this a little more quickly than maybe we otherwise would have.

I thought it was quite cool, Tom Martin stood up and asked a question to the kind of panel, because it was a discussion about ‘would you do a CAR-T or would you do a bispecific?’, and he actually stood up and said, ‘hey, you know, I’ve now got a number of patients who are out five years after their CAR-T therapy, and five years out after their bispecifics, do we think we’ve cured these patients, or do we think the disease is going to come back?’And then if we do, you know, think that it’s potential to cure, should we be putting them together?’ And then there was, as you say, all of this discussion about, you know, do you do your CAR first or do you do your, your bispecific first? Does it matter? And kind of what happens. I’m not sure anybody has a true answer.

I like the debates, so it’s good to see people taking false positions and then debating the data. And so, I kind of think, the idea of targeting biology versus risk stratification, it’s the same idea, and surely you should take both approaches. But it is very interesting that when you think about it, what we’re doing is targeting plasma cell biology and not subsets of the disease, but it doesn’t mean that you should drop one approach.

I thought an interesting aspect of that debate was that it’s easy, I think, to confuse being able to recognize that myeloma is heterogeneous and that we can identify different groups. I think that’s different from risk stratifying when we try to treat or cure. I think it’s easy, for me, when I was listening to the debates, it was a little bit, you know, it was easy to let those two concepts overlap. We can certainly stratify myeloma in many different ways. But the question as to whether or not in our ultimate sort of, you know, endeavor to cure the disease, whether we should be, you know, whether the current way we look at it is truly the right way.

Now, I guess moving topic a bit, I saw the Moffitt team presented some really great data about side effect management of these bispecifics and these CAR’s, and it was really kind of real-world data. Lynn had some too, about kind of, I guess, not being able to predict who’s going to get the side effects, but also highlighting that you can use these approaches in patients with renal failure, even patients on dialysis, which I thought is really important. But also, that we probably shouldn’t be having an age cut-off, and that it didn’t seem to be that older patients had worse side effects with either approach. And it was actually, in some instances, that older patients may be actually had a better run of it, which probably might be because you’ve picked your better older patients, I don’t know, but it was certainly tantalizing that we shouldn’t be having this strict kind of, ‘oh, you’re old enough or not old enough’ for CAR-T.

So, that’s it for this year’s iwMM here in Miami, I think we had a great and optimistic meeting. Thanks for your input, guys. And I look forward to seeing you here next year.

Thank you. So wonderful. Thank you very much.