麻豆传媒

Data presented at the American Society of Hematology (ASH) annual meeting highlighted advances in B-cell maturation antigen (BCMA)-directed therapies, including ABBV-383, a bispecific antibody with reduced toxicity and outpatient potential, and anitocabtagene autoleucel (anito-cel), a CAR-T with high response rates and fewer neurological side effects.

麻豆传媒 brought together three expert leaders in the field: Moderator Joseph Mikhael, MD, is joined by Amrita Krishnan, MD, and Tulio Rodriguez, MD, all of City of Hope, for a virtual roundtable discussion. This third of four exclusive episodes focuses on the future of BCMA-directed therapies in myeloma.

You can watch parts 1 and 2 here.

Following is a transcript of their remarks:

Mikhael: So the third topic I'd love to have a bit of a conversation, and this could take a long time, so we'll have to keep it brief, but really all of the sort of newer approaches to what we've been using in CAR T-cell therapy and bispecific antibodies. And particularly we're interested in two molecules. One was the artist formerly known as ABBV-383 as a new bispecific antibody, and then anito-cel as a CAR-T. So let's start with the bispecific, Tulio. What was your take on that new bispecific antibody that was presented here at ASH?

Rodriguez: Well, I was fascinated by that presentation as well because it has taken this bispecific from a place in where the median survival was very challenging initially. I remember when this whole field started with the AMG 420 and where the half-life was so short that patients needed an IV continuous infusion and a pump that had to be switched every 48 hours, just to jump into now a molecule that you have the option of giving it every 3, 4 weeks and you find as an effective molecule. I mean, I think that is fascinating and I think that is a real event for those who believe in bispecifics.

Mikhael: Absolutely. I agree with you. I think the fact that it can be given less frequently, it really does look like we may see lower rates of cytokine release syndrome and so on, partly because I think of the way it interacts with the T cell, it doesn't bind to it as permanently or as tightly.

And then, of course, that they either use no, or maybe one, step-up dose, I think is going to make it much more convenient. As we always say, 80% of myeloma is treated in the community, only 20% in academia. And so to see it go into the community, we're going to need to be able to do it as an outpatient need, to do it less frequently. I think we're going to see that.

The other molecule that really struck me was the anito-cel study from Arcellx and Kite, looking at really another CAR T-cell therapy and some might say, well, how many more CAR T's do we need? Well, we need more because we need to give them more effectively and give them more safely.

Rodriguez: Less toxicity. Yes.

Mikhael: Yeah. And what struck me about this one was, of course, the response rate was way over 90%, but also that they did not see any delayed neurological toxicities. And we know that's a bit of a concern that we have with cilta-cel [ciltacabtagene autoleucel; Carvykti]. I mean, it's such an effective approach, but we still see some of these patients with delayed neurotoxicities. Let's get your take on that.

Rodriguez: Absolutely. That was very well received because neurotoxicity can be devastating. The only thing that you need to do is to see one of these patients when they start developing this symptomatology, it is really devastating. So I was very pleased to see an effective CAR T that at the same time has such a nice toxicity profile. So I think that I share your sentiment, we need more CAR T-cell products, especially those with less side effects.

Mikhael: Yeah, no, I completely agree on it, we could talk about so many of the things coming, but for us to see so many of these bispecifics now and used in combination to see different strategies and approaches and even completely new molecules, new approaches, like we saw with iberdomide and mezigdomide as CELMoDs [cereblon-modifying agents]. I think the future of myeloma is as exciting as we've seen, in terms of novel approaches.

Rodriguez: Very bright.

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