VIDEO: Future of bispecifics, CAR-Ts and new therapeutic strategies in multiple myeloma

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I think first, we're already seeing that CAR Ts have now moved to one to three lines of therapy. We're excited to see how bispecifics will do in one to three lines of therapy. Those phase III studies are actively accruing. Some have actually probably finished accrual, and we're awaiting readouts. We'll need those phase III studies, right? Because right now, bispecifics only had of accelerated approval. So we need the pivotal registration studies to get full approval of these products, and that's gonna be needed to get patients access globally, so talk about something changing in the future. We can't have these bispecifics be limited to, you know, western industrialized countries because there's a lot of myeloma globally that needs to be treated. So having these phase III studies is gonna be huge for those.

We're also gonna be excited about combination strategies, right? So right now, we're doing monotherapy but combination strategies. We're also excited about fixed duration therapies, right? Can we take advantage of these amazing, deep, durable responses to say, "You know what? We're actually gonna stop your treatment and give you a break," because we never did that before in myeloma. Everybody got treated forever, maybe a little bit less or a little bit more, but that's an amazingly exciting option for patients to say, "You know what? You've had a great response. We can't detect any disease. We're gonna give you a break. We'll monitor you, of course, but go enjoy time and get away from us, right? And have fun." So I think those are some of the areas that we're really looking to improve, and I would say we also need to do more work in a couple of areas.

I would say sequencing is an unmet need. We know that when you go from bispecific to bispecific, probably the T cells are exhausted, and whether we can change that by reducing the frequency, reducing the schedule, reducing the duration of therapy, might that then allow the next bispecific to work better? Should we use new agents in between bispecifics to help with the reactivation? And then also the unmet needs are ISS3, extramedullary as we talked about high risk. So we have a lot of areas of opportunity that we need to improve on, but no question, these drugs are yielding amazing responses.

And I would highlight in particular, one other unique area is we know that CAR Ts are amazing for SLTA cell in particular, PFS of almost three years responsive in 98%. But if you go into that with uncontrolled disease, you have a lot more side effects. So a great use of GPRC targeting therapy like talquetamab is you collect your T cells. So this is important that people don't try to give bispecific before CAR T, but once you've collected the T cells for CAR T, then you can give GPRC as a bridging therapy to control the myeloma and knock it down so that, when you do the CAR T, it's safer and more effective. So I think that's also a really exciting opportunity for patients. So the future is incredible, I think, and super excited to see all these new data emerge when their studies are ready to read out.

I should add two things to the future directions, too. So changing the molecule. So for example, there's some products that make the T cell affinity lower, which might improve the side effect profile of cytokine release syndrome, for example. There's also trispecific agent under development where you have both GPRC5D and BCMA being done at the same time with CD3, and so the question is, can that give you potentially better safety? 'Cause you're giving two different antigen targeting at the same time. Does it improve progression-free survival? 'Cause you're delaying relapse, 'cause you're doing two different antigen, things that we're looking into, and then also, there's agents targeting NK cells in myeloma. So those we're also looking to see, which preliminarily seem to be quite safe. The efficacy, of course, needs to be determined, but really exciting new therapeutic strategies also being explored in myeloma.