Understanding the Use of Bispecific Antibodies in Multiple Myeloma

Bispecific antibodies are a type of immunotherapy treatment which has generated responses across multiple clinical trials for patients with multiple myeloma, according to the International Myeloma Foundation website, which goes on to add that these kinds of agents bind to two different types of cells; one part of the agent attaches to the myeloma cell and the other binds to an immune cell to attack the myeloma cell directly.

Because of the dual attack modality, these agents are more effective than traditional therapies at aiding the immune system to find and kill multiple myeloma cells. Moreover, as the website stated, bispecific antibodies continue to be evaluated across numerous clinical trials, including those for relapsed/refractory and high-risk disease.

To delve deeper into the conversation about treatment with bispecific antibodies in multiple myeloma, Dr. Surbhi Sidana provided a presentation on the topic at a CURE Educated Patient® Summit on Multiple Myeloma, which was hosted on March 22, 2025.

Sidana specializes in the treatment of multiple myeloma and related disorders and is an associate professor of Medicine at Stanford University, in Stanford, where she also leads the Myeloma CAR-T/Immunotherapy program at Stanford.

In the presentation she covered the current landscape of disease and treatment, as well as went over the safety and efficacy of currently approved FDA bispecific antibodies products.

Understanding the Currently FDA-Approved Bispecific Antibody Therapies

“The currently-approved bispecific antibodies in multiple myeloma are approved in very late line myeloma, after four prior lines of therapy, including a proteasome inhibitor ... an IMiD (Immune-mediated inflammatory diseases) ... and an anti-CD38 antibody,” Sidana explained in her presentation.

Tecvvayli (teclistamab-cqyv), she continued, was one of the first bispecific antibodies which was approved for this patient population. The agent received regulatory authorization based on data from the phase 2 MajesTEC-1 trial, a single-arm study which evaluated patients with heavily pretreated disease, most of which had already received a median of five prior therapies.

“[Tecvvayli] was highly effective. Two-thirds of the patients responded, and most of these responses were very deep responses, including complete responses,” she emphasized.

Looking to the clinical outcomes with Tecvvayli, the overall response rate was approximately 67%, with a significant proportion of patients achieving deep responses, including complete responses, Sidana emphasized. Compared with historical data, Tecvvayli demonstrated a near-tripling in efficacy, as older data showed a median progression-free survival of three to four months.

Median progression-free survival exceeded one year, highlighting the clinical benefit in a population with limited treatment options. These data underscore the utility of bispecific antibodies in relapsed/refractory multiple myeloma, particularly in an era preceding widespread availability of CAR-T cell therapies, Sidana explained.

“The median progression-free survival was a little over a year for this bispecific antibody,” she stated, adding that, “Response rates for Tecvvayli were over 70% with both the weekly and every-other-week dose, and the progression-free-survival was eight months to approximately one year.”

Talvey (talquetamab-tgvs) is another FDA-approved bispecific antibody available for the treatment of patients with multiple myeloma, and instead of targeting BCMA, it targets GPRC5D which is expressed on myeloma cells. However, it is also expressed on some normal tissues as well, including the skin, nails and taste buds; this contributes to the unique side effect profile observed with Talvey.

The treatment binds one part of itself to the patient’s immune cells and another part to GPRC5D, in turn, destroying the cancer cells. Notably, the agent was evaluated in a clinical trial for patients with relapsed/refractory multiple myeloma who had received at least three prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody.

Regarding its efficacy, Talvey was evaluated across two dosing schedules: the weekly dosing schedule and the every-other-week regimen, with the latter showing slightly superior outcomes, and both dosing regimens exceeding a 70% response rate.

“The response rates were over 70% with both the weekly dose and every-other-week dose, and the time to progression ... was about a year with the every-other-week dose,” Sidana emphasized.

Finally, the third FDA-approved bispecific antibody that she mentioned in her presentation is Elrexfio (elranatamab-bcmm), which is a bispecific antibody targeting BCMA, similar to Tecvvayli. The MagnetisMM-3 trial evaluated the efficacy and safety of the agent by treating eligible patients with a step-up dosing regimen, followed by weekly doses for six months and then every other week. Notably, during the presentation, Sidana said that the efficacy of the agent was similar to that of Tecvvayli, with approximately two-thirds of patients responding to the treatment. Another one-third of patients achieved a complete response and most of the patients had deep responses to treatment.

Regarding progression-free survival, patients experienced a median progression-free survival of a little over a year, which is consistent with findings from other studies on BCMA-targeted bispecific antibodies, and consequently, reaffirmed the durability of these responses.

Side Effects of the Agents and the Future of Care

Looking first to treatment with Tecvvayli, the toxicities associated with treatment were severe, according to the presentation. Cytokine release syndrome occurred in approximately two-thirds of patients, however, Sidana explained that most cases were low-grade and manageable. Neurotoxicity was also observed in patients at less than 10%. The most prevalent and clinically significant side effects were hematologic toxicities, she explained, including cytopenias and associated infections.

Talvey also had a distinct side effect profile due to its targeting of GPRC5D, which is also expressed in normal tissues, leading to several dermatologic and sensory side effects, such as rashes, dry skin and brittle nails, with some patients experiencing nail loss. Patients also experienced taste changes, as taste buds also express GPRC5D, resulting in dysgeusia and weight loss.

"Talvey... has a lower infection signal compared [with the other FDA-approved agents]. It does have a different side effect profile, which includes ... skin-related side effects like rash or dry skin. And this starts out very commonly. Early on, patients can have nail changes. The nails become brittle. The nails can sometimes even fall off. Taste changes are very common because taste buds also express GPRC 5d and due to these changes, patients often experience weight loss."

Finally, looking to Elrexfio side effects, patients had a high risk of infection with treatment, especially serious infections, which were noted in about half of the patients, with grade 3 or higher infections being a significant concern. Despite the infections, the overall safety profile of the agent aligns with that of other bispecific antibodies.

Sidana concluded her presentation on the topic of bispecific antibodies by saying this:

“Do we need to give these antibodies every week forever? I think the answer to that is very clear to us. It's no, but the details of that are emerging. I think reducing the frequency of antibody administration, we have seen the responses maintained, perhaps even better, but the toxicity is reduced with lower infections, with BCMA, by specifics, lower rash and taste changes. These are lessons we have learned from other bispecific antibodies.

“[Investigators] found that when they reduced the frequency of [treatment], the immune cells that do the magic here, were less exhausted. [This way] you're not beating your T cells all day, all the time, you're giving them time to rest, and they come back renewed and rejuvenated to better kill the cancer cells, and the effectiveness is not impacted.”

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