Target Switch and High-Risk Cohorts Support Talquetamab Use in RRMM

Omar Nadeem, MD
Clinical Director, Myeloma Cellular Therapies Program
Dana-Farber Cancer Institute
Instructor in Medicine, Harvard Medical School
Boston, MA

KEY TAKEAWAYS FROM OMAR NADEEM, MD

1. Talquetamab demonstrated high overall response rates in patients with multiple myeloma who had prior T-cell redirection therapy targeting BCMA.
2. In younger patients now receiving high-intensity quadruplet regimens, there is a pressing need for new later-line therapies.
3. Using biomarkers to better understand factors such as T-cell exhaustion and BCMA resistance could help select therapy in the future.

DISCUSSION QUESTIONS

• What is your reaction to the MonumenTAL-1 (NCT04634552) efficacy data for talquetamab (Talvey)?​
• How do the efficacy (eg, depth and duration of response) compare with other therapies used in the later-line relapsed/refractory multiple myeloma (RRMM) setting?​

Omar Nadeem, MD: What is your reaction to these data? What data points stick out to you the most? How do you think the efficacy is compared with other therapies used in the later-line RRMM setting? Does it look pretty good?

Peter Georges, MD: One thing which strikes me is the response [targeting GPRC5D after] targeting B-cell maturation antigen [BCMA] one after the other. I was at least unaware that two-thirds of those patients [with prior T-cell redirection therapy did respond to talquetamab]. It's amazing. I know it will be short-lived, but there are so many young patients with myeloma who are coming in. I had this 41-year-old patient, and the other day I had a 48-year-old patient. They have their whole life left, and we are using quadruplet up front, so certainly we need these kinds of data where we have something to offer when treating this patient. I really like that piece of information in this trial.

Eric Bravin, MD: These are really positive data. There was a group [of patients with at least 1 extramedullary plasmacytoma] only had a response rate of [over] 40%, but that group with prior generations of drugs may have single digit or 10% to 15% response rates. Even those numbers, relatively speaking, are good.

Nadeem: Yes, I agree. It’s better than anything else that we still have, and it's an approved agent. We're not even talking about a clinical trial drug, so it's great to have that option for patients. But I think the challenge right now for all of us is that we're shooting in the dark. We have patients who go on to these therapies that we're giving and hoping that they respond. There's no biomarker to guide us. We talk about T-cell exhaustion, for example. We have a lot of T-cell exhaustion markers, but we can't routinely check for them in the clinic. It’s not like we can assess someone's T cells and decide, should we give them a T-cell–redirecting therapy next or not? I think that's a pertinent question.

There are soluble BCMA assays, but it's not something that is routinely being done in clinic. Most of the time you don't lose BCMA [expression]. So, you can still give a second BCMA agent, but the mechanism that you target BCMA with may not be as functional anymore, especially if you have exhausted T cells. Belantamab mafodotin [Blenrep] is also a BCMA-targeted agent, but it's an antibody-drug conjugate. It's not a T-cell therapy, so if you have BCMA, you can get a different way of delivering using that same antigen. These are some of the things that we need to figure out, the more of these [therapies] that we have in clinic. Right now, a lot of people are getting either a BCMA bispecific or chimeric antigen receptor T-cell therapy, and then getting talquetamab. That's the most common scenario that I see in a lot of practices.

_Reference:

_{Rasche L, Schinke C, Touzeau C, et al. Long-term efficacy and safety results from the phase 1/2 monumental-1 study of talquetamab, a gprc5d×cd3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. Presented at: 29th European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P915. Accessed November 20, 2024. https://library.ehaweb.org/eha/2024/eha2024-congress/420979/leo.rasche.long-term.efficacy.and.safety.results.from.the.phase.1.2.html}