A roundtable discussion, moderated by Thomas Martin, MD, Blood Cancers Today Associate Editor, of the University of California, San Francisco, focused on bispecific therapeutics for the treatment of multiple myeloma. Dr. Martin was joined by Ajay Nooka, MD, MPH, FACP; Ajai Chari, MD; and Angela Dispenzieri, MD.
In the first segment of the roundtable series, the panel discussed the FDA-approved bispecific agents for myeloma and how the options performed in clinical trials.
Dr. Martin: We’re going to go over a few things about bispecifics. I think let’s start off with an overview. These really have changed the platform in our treatment paradigms for patients with multiple myeloma, thankfully. It’s really been quite a welcome addition to our armamentarium. We have three now that are currently approved in multiple myeloma: teclistamab, talquetamab, and elranatamab. All actually I think have really a nice story in terms of the FDA approval. I’m curious, Angela, maybe you can tell us a little about teclistamab. What impresses you about teclistamab currently in the relapsed setting?
Dr. Dispenzieri: It’s the first in class to be approved, so we have the most experience with it. It was a kind of a revolution, something new to help patients, the strategy and the overall response rates, the ability with the step-up dosing to reduce toxicity. The ability to use it, transition patients pretty rapidly to outpatient especially we have a remote monitoring thing that we can talk about later. But really it’s the responses and the durability of responses that we’re seeing. Looking forward to seeing it move. Where is it after fourth line or can we get to second line?
Dr. Martin: Correct. I love it in our meetings where we show our “old drugs” like lenalidomide and pomalidomide and carfilzomib and we see the baseline single-agent response rates in the 20% to 30% range.
Dr. Dispenzieri: Right and here you are 60% and beyond and CR [complete response] rates 40% and duration of response 18 months. It’s amazing.
Dr. Martin: It really is amazing. I tell people locally and a lot of my patients, for us, it’s been available since December , so maybe eight or nine months. I don’t think there’s been another drug that’s been approved where we’ve treated so many patients with that single-agent drug over the last eight to nine months. We’re approaching 60 patients treated at UCSF with teclistamab, which is really amazing. What other drug have we basically put that to the road test so quickly and now we’re seeing hopefully some more real-world experiences with the drug, which is great. We also have talquetamab, Ajay, what do you think about talquetamab? What impressed you most about talquetamab?
Dr. Chari: Well, 60 to a 100 is the new 20 to 30. The response rates, I think what’s unique about all of the bispecifics is that they are off the shelf, right? Because we also have the CAR-Ts [chimeric antigen receptors) that have been amazing, but the truth is a lot of the rapidly progressing patients can’t wait for those elusive CAR-T slots and the manufacturing. That’s I think the number one benefit of bispecifics, all three of them. But then talquetamab is unique and in that it’s the only bispecific approved that’s targeting GPRC5D, which is a novel target; the genes expressed on 12P and the drug similar to the other bispecific has step-up dosing and then the response rate is around 70%. The PFS [progression-free survival] for the every two week dosing is actually 14 months, which is amazing for an off-the-shelf product.
The toxicities, which we’re going to talk about more, are unique and non-overlapping with other drugs, which also makes it a great combination strategy. I think the other unique thing about this was one of the cohorts that led to the accelerated approval was also in patients who had prior T-cell redirection therapy. Even in those patients, the response rate is over 60%. I think we need to do more work with sequencing and I’m sure that’s an area that we’ll talk about, but I think it’s nice to have a non-BCMA option for our patients that are clearly in need of this drug. I think it speaks to how quickly these studies have accrued because there’s so few drugs for patients who’ve already had BCMA or are looking for a non-BCMA option.
Dr. Martin: Yeah, the worry with all of this is that patients do experience disease relapse. What’s next, right? What is their next thing? With BCMA, we now have what’s next at the current time. Now I’m going to ask you in a little bit, is there a reason to use GPRC5D before BCMA and see what you say? But it’s really exciting to have a new target. Dr. Nooka, you actually had a lot of experience with elranatamab in the clinical trial. Tell us what impressed you about elranatamab?
Dr. Nooka: Elranatamab is a second BCMA bispecific antibody that was approved. We have a great experience with teclistamab as Dr. Dispenzieri explained. Elranatamab, what impresses me the most are the response rates, similar to what was expected for any BCMA bispecific antibody, where the toxicities of so predictable. If you look at the safety, the safety is all in alignment with what we expect from a bispecific antibody. But being the second in the game, we already have a steep learning curve with the first agent, so you expect the toxicities to be mitigated drastically. That’s what we have seen in terms of the lower risk of infections, in terms of the CRS [cytokine release syndrome] and all those are to be, we were well prepared for when we got the elranatamab in place. It’s a very exciting time. More is good. I hear that more is not good at times, but we have two CD38 antibodies; we have two BCMA-targeting CAR-Ts; we have two BCMA-targeting bispecific antibodies. The more that you delve into the combination space, there are things that the signals that you can expect from these different combinations really open up doors for us for wider research. That’s what excites me the most.
Dr. Martin: So more is always better. I completely agree with you in terms of that.