IMS 2025: Advancing Immunotherapy with Costimulatory Bispecific Antibodies in Multiple Myeloma

In an interview with Pharmacy Times®, Karen Rodriguez-Lorenc, MD, therapeutic area lead of hemato-oncology at Regeneron, discussed the potential of costimulatory bispecific antibodies to enhance multiple myeloma treatment by driving deeper and longer-lasting responses beyond what current therapies achieve. She highlighted her presentation, “9 Next-Generation Immunotherapies for Relapsed/Refractory Multiple Myeloma (RRMM): Integrating Costimulatory Bispecific Antibody (bsAb) Signaling,” which she shared at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada.

Rodriguez-Lorenc explained how these next-generation immunotherapies differ from existing bispecifics by adding a second signal, CD28, to boost T cell activity while aiming to maintain safety. She also highlighted their potential role in sequencing strategies, offering flexibility in combining or adjusting treatment to help patients who have exhausted standard options.

Pharmacy Times: Can you start by introducing yourself?

Karen Rodriguez-Lorenc, MD: My name is Karen Rodriguez-Lorenc. I'm the therapeutic area lead for hemato-oncology at Regeneron.

Pharmacy Times: What makes costimulatory bispecific antibody signaling an exciting next step in immunotherapy for relapsed/refractory multiple myeloma?

Rodriguez-Lorenc: So what we have, as of now, is that multiple myeloma treatment is improving, and it's changing a lot, but still there is room for improvement. The T cell engagers and CAR T have brought an amazing improvement in the management of these patients, but still there is room for having deeper responses and longer duration of response. These tested engagers and combinatorial activities that we are trying to pursue with costimulator agents are intended to give us even deeper responses and longer control of the disease.

Pharmacy Times: How do these next-generation immunotherapies differ from currently available bispecifics in terms of mechanism and potential clinical benefit?

Rodriguez-Lorenc: Let me explain a little more about the format of these bispecifics and what the targets are. The T cell engagers, in the case of linvoseltamab for example, have two different arms. One is going to the BCMA, which is the target of the multiple myeloma cell, and the other arm is connected to the CD3, which is the target of the T cell. What it does is increase the activation of the T cell and permit the killing of multiple myeloma cells. That is what we call signal one.

As you know, sometimes when these patients are exposed to these therapies, what we observe is a dysfunction of the T cell. The intention with the costimulatory is to target a different multiple myeloma target, which in this case is CD38, well known as a monoclonal antibody in the treatment of this condition. The other arm is CD28. The intention of CD28 is to increase the activity and efficacy, but hopefully also maintain safety. All in all, this is trying to enhance the activity of linvoseltamab, for example, as a T cell engager.

Pharmacy Times: What safety or tolerability challenges do you anticipate with costimulatory bsAbs?

Rodriguez-Lorenc: This bispecific, the costimulatory, does not have efficacy or activity by itself. You need to have a signal one in order to enhance the activity of the T cell. So what we are expecting is that the safety profile will be consistent with what we already know, for example, with linvoseltamab. We expect it will be similar.

Pharmacy Times: How might these agents fit into sequencing strategies for RRMM, particularly for patients who have exhausted standard options?

Rodriguez-Lorenc: As you know, for relapsed/refractory multiple myeloma, there are all these new agents, such as lymphoma and CAR T therapies and other bispecifics. The expectation is that costimulatory agents can be used for rescuing some of those patients who were already exposed to those therapies.

With these two drugs, we can also have some flexibility on how to manage them. Do we need to combine them always, or can we turn on and off the signal depending on the need? If the patient is progressing, should we combine the CD28 to see if we can increase the activity, and then, when you control the disease, switch it off and turn off that signal? I think the beauty of combining these two different bispecifics is the flexibility they give you for different regimens.