Key Takeaways From RedirecTT-1: Teclistamab + Talquetamab in Relapsed/Refractory MM

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Expert perspectives on the real-world use of combination teclistamab and talquetamab in patients with relapsed/refractory multiple myeloma.

Transcript:

Ajai Chari, MD, PhD: So, Dr Schinke, what are your thoughts about this RedirecTT-1 [trial], and where do you see this being used?

Carolina D. Schinke, MD: I think the results are very impressive. I mean, response rates over 90%, I don’t think we’ve seen that in single-agent bispecific treatment, so I think, as Dr Cohen presented, we were all impressed with the results of the data. Obviously, also for this patient population with EMD [extramedullary disease], as you mentioned, [an] unmet need, because they do really badly, had excellent response rates. So I think it definitely is a very attractive regimen for these particularly high-risk patients that historically don’t do well. Obviously, we’ve then also seen adverse events. You have then both infections and skin and nail changes, dysgeusia. So, again, [it] will be a little bit of a balance of who needs it, who will really benefit from it. But overall, I think the results are very impressive.

Ajai Chari, MD, PhD: I agree. I think what’s particularly striking is, again, we always need to have caution with cross-study comparisons, because this is 4 lines of therapy treated in Europe versus the MajesTEC-1 and MonumenTAL-1 [trials], where the US treated more lines of therapy. I think what’s a very telling sign is the response is really 96%. And while we compare [it with] CAR T [chimeric antigen receptor T-cell therapy], the big, big difference with CAR T, of course, is this is off the shelf. All those rapidly progressing patients that you don’t even get signed consent to CAR T, or may not even get through bridging, may not get to the infusion of CAR T, those patients are all being treated on these off-the-shelf products. So to be having this kind of response and durability is really compelling. Obviously, we’ll need to have a direct head-to-head comparison with other products. I think having non–CAR T options for heavily treated patients is really exciting. The other signal, I’m curious to get your take on it, but I think there’s a hint that this is going to be better than monotherapy because if phase 1, if all the cohorts had a PFS [progression-free survival] of around 20 months, and it’s not even reached with the RP2D [recommended phase 2 dose]. I think that really bodes well for the PFS being probably better than [with] monotherapy. But I’m curious to hear your thoughts since you presented MonumenTAL-1. Which one do you think is going to pan out better in the future?

Carolina D. Schinke, MD: I mean, absolutely, these results were, even as you mentioned, you shouldn’t cross-compare, but the difference is just so striking that it seems to be just much better than single-agent [therapy] or monotherapy. In a way, it’s a little bit surprising because you would think that BCMA [B-cell maturation antigen] or GPRC5D is just so strongly expressed in plasma cells. So how do you get that extra efficacy when you think it should be targeted already by monotherapy? It would just be interesting also to understand a little bit about the biology pathophysiology and see what makes it just so much more effective. But again, I think for these patients who otherwise would just have poor results, and we’ve seen EMD or those with plasmacytomas on monotherapy with these bispecific antibody treatments, don’t do so well. It was mostly those with no plasmacytomas, and no EMD that had these overall response rates of 70%, 80%, but not those with EMD. Here, combining teclistamab and talquetamab, even for those with EMD or plasmacytomas, had over response rates of 80%. So I think that’s very striking.

Ajai Chari, MD, PhD: I agree. I think, of course, we are seeing the toxicities from each agent, which then breaks up who would we give combinations to. I think as you alluded to, because monotherapy responses are quite high, especially with teclistamab, with the DOR [duration of response] being 18 months, which is one of the beautiful things about teclistamab. The struggle of that infection, to me, I think what this raises is that perhaps you can be thoughtful about picking those unmet needs from monotherapy, such as ISS [International Staging System 3], bulky disease, extramedullary disease, or maybe even prior T cell redirections, right? Those unmet needs might be the patients for [whom] you do combination therapy. And finally, these are clinical trials. In the real world, we have the beautiful advantage, especially in the US, of kind of doing what we want. This means that you can start with monotherapy, and if you’re getting a CR [complete response], you don’t need to add the second drug. But if you aren’t getting that, maybe you can then introduce it.

So you don’t need to do this for everybody. Because the responses are so rapid and so deep, you can kind of risk-stratify patients by how they’re doing. And I think the final point is, can we now use this really powerful efficacy to mitigate some of the toxicities, right? Which is we’re still very early. They tried to hit the RP2D. But one of the things I wonder about is, I think with BCMA bispecifics, there are a lot of questions about what is the right dose and schedule and duration, right? We think that because the durability is so good, maybe we can do a fixed duration. When you have another bispecific that you can give more without this continuous increase in infection, maybe that’s a way of cutting the BCMA duration shorter. Conversely, with the GPRC, maybe since you have the BCMA bispecific boosting your efficacy, maybe you don’t need these higher doses and you can get away with less drug. As we discussed earlier, if the dysgeusia is dose-related, maybe you don’t need such a high dose. So, I think we’re just at the beginning of these really early combination data, but I think it’s really exciting and promising. I’m just curious to hear, do you have any other thoughts on this or maybe on CRS [cytokine release syndrome] management with the combinations? Any concerns or thoughts on that?

Carolina D. Schinke, MD: No, I think it’s encouraging that the CRS rates are not higher in combination therapy. Also, the grading is again, 17%, grade 1. Mostly it seems very manageable. I would agree with you that the dosing schedule probably can be adjusted. It can be really individualized, and that’s really a nice thing. We want to have rapid response, especially for those with EMD, maybe life-threatening plasmacytomas or myeloma disease. We want a rapid response. So probably we’ll start high with high doses and an every-other-week dosing schedule. Once they achieve a response, probably you can back off a little bit. And I think that will be really the beauty about using these bispecifics, that you can individualize treatment in a certain way based on efficacy, on [adverse] effects. So, I think there’s a lot to come.

Ajai Chari, MD, PhD: I couldn’t agree more.

Transcript edited for clarity.

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