Physicians Share Perceptions of BCMA-Targeted Therapies for Multiple Myeloma

Carol Ann Huff, MD

Associate Professor of Oncology

Johns Hopkins University School of Medicine

Medical Director

Johns Hopkins Kimmel Cancer Center

Baltimore, MD

DISCUSSION QUESTION:

• Are you familiar with the phase 1/2 MajesTEC-1 clinical trial (NCT04557098) of teclistamab-cqyv (Tecvayli) and its results?
• What are your perceptions of this trial and this bispecific agent?

CAROL ANN HUFF, MD: What are your perceptions of what you know about this trial and where you might see teclistamab in your line of therapy for patients?

JAVIER MEADE, MD: For this population of patients, this is very effective. To me, reaching MRD [minimal residual disease] in somebody who is on their fourth line or fifth line [of therapy] is very impressive.¹ The overall response rates were very high, all things considered. At least for this study, for this particular report, this is a very effective therapy. In my mind, the results are way better than what the New England Journal of Medicine reported on [idecabtagene vicleucel [ide-cel; Abecma] CAR T-cell therapy, in my perception.²

HUFF: How do you see [using] teclistamab versus CAR T cells in your patients?

GOCKE: I didn’t see it this way in the beginning, but after more discussion and then seeing other patients, the first thing I think of when I see teclistamab now is [risk of] infection.

IKECHUKWU AKUNYILI, MD: I think that over time, teclistamab will be doing a lot more. Most of us would think of it even before CAR T cells, the main reason being that it’s off the shelf and you don’t have to wait for the manufacture. [If] the patient is already penta-refractory, you’re going to think of what to do to hold them while they are progressing to wait for CAR T-cell therapy and production of the CAR T cells that with time we are going to end up using more teclistamab. I expect that talquetamab will probably be approved…so we will have new options.

DISCUSSION QUESTION

• What are your thoughts on sequencing later-line therapies and using bridging therapies to CAR T-cell therapy?

HUFF: If there is a patient who you are planning to take to CAR T cells but you need bridging therapy, teclistamab or another BCMA [B-cell maturation antigen]-targeted therapy preceding a BCMA CAR T-cell therapy is not a good idea, but talquetamab, which targets…GPRC5D, or another bispecific along those lines, might an option in a bridging phase.

There are data coming out. None of the trials of teclistamab or ciltacabtagene autoleucel [cilta-cel; Carvykti] or ide-cel initially allowed other BCMA therapies, so those trials don’t have it.^1-3 But the talquetamab data and that of some of the other emerging bispecifics do have patients who’ve had prior BCMA therapy and there is response, some higher than others, but it is probably not the best bridging modality.⁴

I’m not saying that’s what [Dr Akunyili] was suggesting, but I wanted to make that point so [everyone] would be aware. I agree with [teclistamab] being off the shelf. As CRS [cytokine release syndrome] and these adverse events become easier [to manage], physicians have become more comfortable managing them…[so] they will be easier to give. The [risk] of infections is definitely real,¹ and some of the other bispecifics, such as talquetamab and others, seem to have lower infection incidence and may have that benefit for patients,⁴ but time will tell.

MAYER GORBATY, MD: Once CAR T cells are produced, do they need to be used immediately or can they be frozen, stored, and used a year later?

HUFF: They are frozen and shipped back frozen, so the products can be stored. The ability to make those cells is the biggest limitation, but they can be stored. The way that the business model works is that the institution is not charged for them until the company sends them back. But they’re not desiring to manufacture them and store them forever just to keep them there.

GORBATY: Could they be manufactured, for example, when you are tri-refractory? So once you fail your fourth cycle, they’re immediately available?

HUFF: The biggest challenge is the ability of the companies to manufacture them right now. Whenever you make them, first line, second line, third line, they don’t have the capacity to make them for everybody who [could receive them].

MEADE: My guess is it’s very likely nobody who works with similar products will be making them too far in advance because if something happens to the patient and the therapy doesn’t move forward, they can’t charge for it, so it’s essentially working for free.

GORBATY: But, of course, we’re losing patients by not being able to manufacture it in time. There would probably be a trade-off at some point.

HUFF: Right. But…they don’t have enough manufacturing slots.… There are efforts ongoing looking in allogeneic CAR T cells using T cells from healthy people as a means of trying to boost that aspect of things, but the challenge is the manufacturing capability. And Dr Meade is right…storing them forever is probably not what they would want.

MEHMET KOCOGLU, MD: One of the things we are also seeing more often is out-of-specification products. Everybody is ready, the patient’s [cells] have been collected, and the manufacturing is going on. All of a sudden you hear from company that they are out of specification because…the product has to meet all of these requirements and sometimes it doesn’t. Some of these products we were able to give through the expanded access under an umbrella protocol, and some of them we cannot even touch because the company will not release it. That is another level of frustration sometimes. Fortunately, that’s not happening very often but nonetheless it happened a few times.

HUFF: I’ve had the same experience where products…even out of specification, have been only a little bit out of specification so they could have been given under expanded access. The companies will release them with the right IRB [institutional review board] approval and so forth.

GORBATY: Do you have a bridging regimen you prefer while you’re waiting for the CAR T cells if the patient requires treatment?

HUFF: I wouldn’t say we have a regimen that we absolutely prefer. We try to stay away from bendamustine because there are some data to suggest that outcomes may not be as good.⁵ When patients are quite sick, we will, at times, resort to giving PACE [cisplatin, doxorubicin, cyclophosphamide, and etoposide] and other chemotherapies for patients in that situation. It’s hard because the patients are all so different.

KOCOGLU: We are doing it a little bit earlier these days, but I had a few patients on PACE regimens, like you said, but that’s of course taking the risk because it’s an intense regimen.

HUFF: We only do that if their disease is progressing rapidly and we have the cells that are being manufactured and we want to get them there, but not by default.

_References:

_{1. Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478}

_{2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614}

_{3. Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8}

_{4. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med. 2022;387(24):2232-2244. doi:10.1056/NEJMoa2204591}

_{5. Iacoboni G, Martin Lopez A, Jalowiec KA, et al. Recent bendamustine treatment before apheresis has a negative impact on outcomes in patients with large B-cell lymphoma receiving chimeric antigen receptor t-cell therapy. Blood. 2022;140(suppl 1):1592-1594. doi:10.1182/blood-2022-169783}