Practical Considerations for Talquetamab Use in Relapsed/Refractory Multiple Myeloma

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Following their review of data from MonumenTAL-1, Ajai Chari, MD, and Carolina Schinke, MD, share practical considerations for real-world use of talquetamab in relapsed/refractory multiple myeloma.

Transcript:

Ajai Chari, MD, PhD: Thanks, Carolina, for a great presentation. Congratulations on being the presenting author at ASCO [the American Society of Clinical Oncology annual meeting]. What do you think for the audience members who may not have had experience with the clinical trials—what do you think of this MonumenTAL-1 study’s updated results, why might they be important for the listener?

Carolina D. Schinke, MD: I think mainly because we have now another treatment option, yes, another bispecific antibody that can be used in our repertoire of treating this heavily relapsed and refractory patient population. So again, obviously, some of the [adverse] effects will be or are concerning to physicians out there who have not been really using bispecifics, particularly CRS [cytokine release syndrome] is quite common. Again, I think as we move along, we are learning how to deal with it. Most of the grading is low, 1 to 2. So, I think it’s becoming more manageable. Just more these kind of [adverse] effects, distinct [adverse] effects of talquetamab are nail changes, skin changes, and taste changes that I think we are going to look more into in the future and how to treat those, especially this dysgeusia, which can be irritating to patients and can even be impairing their quality of life to some degree if they’re not able to taste the food they like. Again, that is something that is of high interest in how to treat it and how to also further quantify it. But overall, I think it’s just going to be another weapon we can use for our patients.

Ajai Chari, MD, PhD: So, I think the dysgeusia, you’ve participated clearly in the clinical trials. I think if we look at the AEs [adverse effects] that are unique to this agent, which you mentioned are dysgeusia, nail, and skin, typically, the skin is early, quite manageable with steroids, and the nail is more cosmetic, and I think most people are concerned about the dysgeusia. How would you weigh that risk-benefit profile for this agent? I think that’s one of the main questions, and you alluded to the quality of life. So what would you recommend to the health care teams [to treat it], we hope? We should mention that talquetamab might be approved later in 2023 in the US through accelerated approval. So what would you recommend to the folks listening or watching about managing dysgeusia? And do you think it would be a deterrent or not? That’s one of the questions that comes up with this agent.

Carolina D. Schinke, MD: Yes, I think that is important. It’s important to discuss it with the patient to expect that [adverse] effect. We have tried different remedies or medicines to maybe counteract dysgeusia, but nothing really works. So we’ve tried steroids, Klonopin [clonazepam]. Some patients even tried medical marijuana or other remedies, and it’s not necessarily that they eat less or lose weight, but it’s just that they cannot taste. What we’ve seen is that in the beginning, and then obviously all the reporting, is very subjective.

So in the beginning when patients who really had no other options start this medicine and see their myeloma responding, it’s like, wow, they’re so impressed that they don’t really care about the dysgeusia, and they don’t even report it to a degree where we really knew about that problem. As long as they stay on the drug, I feel like it became more of a problem because their attitude changed a little bit in terms of, well, myeloma looks good, I’m alive, but I can’t taste anything, and my quality of life is just severely impaired. That’s, I think, where we started having more and more complaints and started to maybe quantify it more, maybe do a little bit more about it. In the end, I think a dosing schedule might also help. Right now as we’ve seen it can be given every other week. Maybe for those patients who have a response, we can even stretch it out to once every month or longer. Hopefully with that, this dysgeusia will improve, because otherwise, I don’t think we have…any idea exactly why patients get it. We think it’s due to taste receptors on the back of the tongue, but it’s also not quite clear. And hence we also don’t have any real measures to treat it.

Ajai Chari, MD, PhD:I agree. At my previous institution, we had a lot of patients on this study at Mount Sinai, and I think first, as you alluded to, sometimes patients are more likely to disclose this to nurses than physicians. Because they’re so worried being a heavily treated patient that we might do something that would disrupt a response. I think I feel like the nursing team is really key in listening to these and helping with the AE management. I was very fortunate to have an outstanding nursing team at Sinai. They presented a poster at [the 2021 American Society of Hematology annual meeting], and at that point, out of about almost 80 patients at Sinai, only one patient had come off for non-progression, which I think is very important, because ultimately, it’s the patient that decides how bad an AE is.

I think the way patients vote is with their feet. If there was much higher rates of coming off study, that would be concerning. I do think the other thing I would add is, it was very valuable for me and my team to have participated in the dose-escalation study because these bispecifics have what we think is a pretty wide therapeutic index. Because I’ve had some patients now out on what I call homeopathic doses, out 4 years on monotherapy of talquetamab. We have to try to find the sweet spot of getting those high response rates without the toxicity. I bring that up, because in our dose escalation, we never saw any of these things at the lower doses. To the point where when we first started getting patients with these things, we actually thought it was unrelated because at that point we’d already treated 30, 40 patients at the lower doses and there was no rash, no dysgeusia, no nail changes. And it was at the higher doses that you started to see this. I mention that because I think, as you alluded to, while we are still understanding—because let’s face it, none of us are familiar with taste.

We don’t even have the tools to really ask and monitor and grade. Probably it has something to do with GPRC expression, either in the tongue or salivary glands. And so we, as I know you’re also involved, we’re engaging experts in dental, ENT [ear, nose, and throat], GI [gastrointestinal] and trying to really get more understanding of the pathophysiology. Because the main way to treat the AEs is to understand the pathophysiology. Since this is so unique in oncology, I think that’s why [it’s] a little bit behind. But the good news, and that’s one of our mainstays of management, is that because the responses are high and rapid, you’re not asking patients to have dysgeusia for 4 months without knowing if it’s working. These patients are responding quickly and deeply. And so then you have the luxury of skipping doses and backing off and reducing. That is…until we figure out the pathophysiology and pathophysiology-directed treatment of these AEs, this is, in meantime, I think a very helpful measure.

Transcript edited for clarity.

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