Evaluating Long-Term Efficacy and Safety Results from MonumenTAL-1 on Talquetamab Treatment for Patients With Multiple Myeloma

Caroline Schinke, MD, Myeloma Center at the University of Arkansas for Medical Sciences, Little Rock, Arkansas, speaks about the long-term efficacy and safety results from the MonumenTAL-1 trials on of talquetamab treatment among patients with multiple myeloma (MM).

Transcript:

Hello. My name is Caroline Schinke. I'm one of the faculty staff here at the Myeloma Center at the University of Arkansas in Little Rock. We treat predominantly multiple myeloma; we see quite a lot [of patients] and we've used bispecific antibodies, including talquetamab, which I'm going to talk about today.

I'm excited to discuss a little bit the long-term efficacy and safety results from the MonumenTAL-1 study of talquetamab, which is a GPRC5D bispecific antibody, and which has now been in clinical trials for the last years in patients with relapsed and refractory multiple myeloma. Talquetamab was approved by the FDA in August 2023. It's now widely used in relapsed and refractory multiple myeloma patients. I think we've seen unprecedented efficacy with this drug. It also has a unique side effect profile, which we're going to mention.

In terms of clinical outcomes, as well as efficacy, most recently Dr Leo Rasche [MD, University Hospital of Wurzburg, Wurzburg, Germany] presented  that talquetamab has efficacy or response rates, overall response rates of up to 70%. This, is from clinical trial data. Talquetamab in clinical trials was studied at 2 dosing schedules. One was a weekly dosing schedule at 0.4 milligram per kg every week, and then the other schedule was 0.8 milligram per kilogram every other week.

Overall response rates for both dosing schedules was 70%, meaning that at least 70% had a partial response or better, which in this heavily-treated and refractory patient population is a very impressive result. Roughly 60% of patients had at least a [very good partial response] VGPR or better. So again, that just confirms or shows that talquetamab is able to achieve deep responses in these relapsed multiple myeloma patients. For patients that do achieve a deep response, like a CR, complete remission, or VGPR, we now also have robust follow-up data.

The duration of response in patients who achieve deep responses was found to be 29 months for patients with a weekly dosing schedule, and has not been reached yet for patients who followed a every other week dosing schedule. So again, that's very impressive. We have deep responses for 60% of patients achieving VGPR or higher. Those patients that achieve such a deep response also have quite a robust and long duration of response. Especially those that achieve a complete response tend to maintain the response for over 2 years. Median progression-free survival for the whole patient cohort that was studied is 8 months; in those that had a weekly dosing schedule it was a little bit longer at 11.2 months [than] in those that had an every other week dosing schedule.

From this data we don't see that every other week dosing schedule is in any way inferior to weekly. I think there might be a thinking or hypothesis that the more you give the bispecific, the better it works. But in fact, it might actually be the other way around. All the data we have so far suggests that the every other week dosing schedule might actually be more effective and certainly also more convenient the patient. They just need to come in every 2 weeks instead of weekly.

These are great results and these are now also matured, long-term results, which we did not have a year ago to confirm and to emphasize the efficacy of talquetamab in relapsed multiple myeloma patients.There was also a sub-cohort in these clinical trials, namely patients that had prior exposure to [B-cell maturation antigen] BCMA-directed treatment. Particularly patients who had prior BCMA-directed CAR T-cell treatment were included in this clinical trial. I think that that's great because it probably represents a real world patient. The real world patients currently because most of them will probably go to CAR-T first before they go to talquetamab. That's reflective of what we do, or what most physicians do in current clinical practice.

Even those patients that had prior CAR-T exposure or BCMA-directed CAR-T exposure had had a good overall response rate up to 65%. It was the as the overall response rate with a VGPR of roughly or better of roughly 55%. And here the median progression free survival in these patients 8 months. Overall great efficacy, especially for patients who achieve deep responses like a complete remission, we have long-lasting responses.

The side effect profile for talquetamab is quite unique. GPRC5D is not only expressed on plasma cells, it's also expressed on keratin-containing cells, so skin cells, nail cells, the taste buds, and on the tongue. Adverse events, hence, includes skin and nail-related changes like rash, nails might come off, and probably what is most concerning and cumbersome to the patient is the taste-related changes, which are likely due to the talquetamab affecting the taste buds. This taste-related changes also called dysgeusia is very common. In this long-term data that was presented recently, we see roughly at least 70 to 80% of patients having dysgeusia. This is something that also starts on very early on.

And so this is currently an ongoing project, how to mitigate this, in particular dysgeusia, this particular side effect. The other adverse events, so rash as well as nail or skin changes as well as nail changes, usually are not bothersome to the patient and resolve pretty well with topical treatment. Sothese are side effects that usually can be dealt with well. And again, don't tend to be so bothersome to the patient. Overall, it's been reported in this abstract that dose reduction or discontinuation because of these adverse events was rather low.

The IMWG criteria have summarized very nicely how to prophylax these patients when they go on bispecific antibody treatment, what to consider for supportive treatment for those patients that go and talquetamab and will likely experience dysgeusia  or skin and nail-related changes. I think moving forward, it still is a discussion between the treating physician as well as the patient on what treatment to use and in what sequence.

At some point there is going to be likely some progression on a bispecific antibody and then you might have to switch to another one or try to bridge them and then switch to another one. There is also currently an ongoing research interest [into] how to sequence these bispecific antibodies, including then also CAR T-cell treatment, which is now expanding and has been approved for relapse after 1 line of treatment. There is going to be a lot of updates in the near future on efficacy and sequencing, as well as how to improve the side-effect profile.