IMS 2025 | Real-world insights into talquetamab dosing patterns for the treatment of myeloma in the U.S.

So I have a poster later today about real-world talquetamab dosing patterns in the United States. You know, the audience is well familiar with talquetamab or talquetamab. Same thing. It’s a GPRC5D targeted bispecific antibody. Works very well in multiple myeloma, you know, easily 60-70% response rates, but does come with a unique set of off-tumor on-target toxicities. GPRC5D is found on skin cells, nail cells, tongue cells, etc. And most patients with talquetamab, over half of them will develop some level of dysgeusia, issues with their taste. Many of my patients have lost weight while they’re on it. Some patients like that, most patients don’t like that, and certainly it’s not planned for the drug to be used for weight loss. People can have skin issues, nail issues, etc. And I think what’s interesting about talquetamab is that at least in the United States, actually, and also in Europe, there’s two approved dosing schedules. There’s 0.4 mg after the initial step-up dosing. You can either do 0.4 mg per kilo body weight once per week, probably every one week, or 0.8 mg per kilo every two weeks. Talquetamab is so new in the US and Europe that we haven’t really developed or seen that much real-world data with it. There are a couple of published papers, mainly from academic consortia, and I’m a member of some of these academic consortia myself, but there are smaller centers and non-academic centers using talquetamab. So this is where sometimes claim-based analyses that are focused on everyone using talquetamab across the country, trying to glean some insights there may be helpful. That’s what we did. We used a large database to look across the country, the United States of all patients getting talquetamab, to kind of see how patients were doing. There’s some limitations there. Updosing, how it was done. I can talk about dosing frequency, and I can talk about time to next treatment, right, in terms of when they stopped using talquetamab in the absence of death or data cutoff. In brief, in the last year and a half since tal has been approved in the United States, still primarily being used as monotherapy and primarily historically having inpatient step-up dosing, but that is starting to change. We’re seeing more outpatient step-up dosing and about 10% of the patients we identified with a cutoff earlier this year were getting tal in combination with the teclistamab or pomalidomide or daratumumab. And indeed, there are very interesting data from the TRIMM-2 study and other studies showing that talquetamab plus daratumumab or talquetamab plus pomalidomide might work very well. I’ve actually had a patient on tal plus pom. Getting insurance approval was a nightmare, but when we got insurance approval, it worked really well. The tal was kind of working and the pomalidomide instantly brought disease down, which is really encouraging. The 0.8 mg per kg every two weeks was a preferred dosing option and in real world setting. And even the patients who started at weekly dosing deescalated to every two week dosing very rapidly. Most patients went down to every once a month dosing, a median of 4.7 months after starting treatment. I think it’s very important because I think the FDA and the EU, the EMA has two approved package inserts, right? Where you can do 0.4 mg per kilo once per week, like every one week, or 0.8 mg per kilo every two weeks. And it’s hard to say which one is better. I think truly 0.8 mg per kilo every two weeks, one is being used more, and two probably honestly is better for a couple of reasons. And I think it’s a very important takeaway for anyone who’s, I’m not quite enough to remember. 1.4 mg per kilo every one week dosing. You’re seeing much more in the way of toxicity, I think, over time because you keep hitting the GPRC5D week after week after week after week. Whereas every two weeks, you kind of give the tongue and skin and nails a chance to recover bit by bit. Two, time toxicity, I think, is real. You know, not a real, you know, it hasn’t been defined that well, but certainly coming in for treatment once a week forever versus every two weeks forever, patients will prefer the latter. And three, really interestingly, in MonumenTAL-1 and the updated data that were presented by Dr Chari and colleagues or published by Dr Chari and colleagues of medicine hematology this year, they had a supplemental table where they looked at patients who did have talquetamab dose reductions versus those who didn’t. They did a landmark analysis to account for the fact that you need to stay on talquetamab to be able to have a dose reduction. Even with that landmark analysis, the patients who had dose reductions or dose de-escalations actually had better PFS than the ones who stayed on treatment verbatim. That probably means that dose de-escalation might actually lead to better efficacy, which seems crazy, less equals more, probably because two things. One, patient’s toxicities are better. They’re able to stay on treatment for more. But two, talquetamab and any T-cell engager does cause T-cell exhaustion, and it may be that dose de-escalation leads to better outcomes because the T-cells aren’t as exhausted with each dose. I can’t prove any of that with our claims analysis real-world data, but at least I can say that if you’re wondering what your peers are doing, most of them are doing every two-week dosing, and I suggest doing the same. I have had patients who want the toughest regimen, right? They think that, oh, doc, like if you think once a week is better, I’ll do it. I’ll come in every single week. I’ll lose all my hair and tongue cells and everything. They want bigger is better. And I think these data help to confirm that actually, no, bigger is not better. Less is more here. Move to every two-week dosing. Honestly, move to every one-month dosing, as toxicities develop, and patients are often able to maintain their response.

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