Bispecific Antibodies in Multiple Myeloma Trials: A Frontline Perspective

The race is on to optimize the use of bispecific antibody dual-targeting therapies in treating multiple myeloma.  

Q: What makes BsAbs such a game-changer in multiple myeloma treatment? 

Dr. Vidal: Over the past two to three years, multiple myeloma treatment has relied on combination regimens—immunomodulatory drugs (IMiDs), proteasome inhibitors and anti-CD38 monoclonal antibodies. These extend survival, but resistance eventually develops. Bispecific antibodies change that equation by activating the immune system in a highly targeted way. 

They bind to two sites: one on T-cells and one on myeloma cells, directing the immune system to attack the cancer more efficiently. We’re seeing real, durable responses in patients who previously had few options left. That’s huge. 

Q: What are the biggest challenges in integrating BsAbs into treatment paths? 

Dr. Vidal: The biggest hurdle is toxicity. Bispecific antibodies can trigger cytokine release syndrome (CRS) and neurotoxicity that may be severe, which means patients often need hospital-based care. That limits access—these aren’t yet therapies that community oncologists can easily administer. 

We’re also exploring combination strategies—can pairing antispecific antibodies with IMiDs, with anti-CD38 monoclonal antibody or other standard multiple myeloma therapies enhance efficacy while reducing toxicity? That’s the next frontier, but we need large-scale trials to validate these approaches. 

Q: Are BsAbs a replacement for CAR-T therapy in multiple myeloma? 

Dr. Vidal: Not necessarily, but they offer a critical alternative. CAR-T therapy is a one-time treatment, but it requires a long and complex manufacturing process. Bispecific antibodies, on the other hand, are ready to use. Though there’s no head-to-head comparison in a clinical trial, in indirect comparison and in the real-world setting the incidence of Grade ≥3 CRS and neurological adverse events was lower in myeloma patients treated with bispecific antibodies compared to those receiving CAR-T cell therapy.  

Yet, using one treatment doesn’t exclude the future use of the other. The efficacy of BCMA-bispecific after CAR-T was explored in clinical trials (KarMMa-2 and IMAGINE) and also in the real-world setting, with overall response rates that range from 45-63%. Elderly patients may have less toxicity with bispecific antibodies.

In the future, we may be able to better characterize the patients who benefit from bispecific antibodies. Talquetamab, a GDPR5D bispecific antibody had 73% response after CAR-T therapy. In MomenTAL-1, it was given as a bridging therapy for patients waiting for CAR-T, demonstrating strong efficacy.  

"These kinds of sequencing strategies could change how we think about myeloma treatment timelines."

Q: What’s next for BsAbs in multiple myeloma trials? 

Dr. Vidal: “There’s not enough data on the sequencing of the different treatment modalities in myeloma. Right now, bispecific antibodies are used in late-stage disease, but we’re seeing a shift toward earlier-line use. If we can bring these therapies into first-line treatment settings, we may be able to extend response durability and improve long-term survival. 

The current marketed bispecific antibodies target BCMA and GDPR5D. New generations with similar targets and bispecific antibody targeting new targets as FcRH5 (Fc receptor-like 5), CD38 and CD138 are under development.  

We’re also focusing more on patient-reported outcomes (PROs). Multiple myeloma patients experience severe symptoms—bone pain, fatigue, anemia, kidney dysfunction—and understanding how bispecific antibodies and other drugs affect their quality of life is just as important as traditional clinical endpoints. 

At the end of the day, we need to balance innovation with accessibility—because a therapy is only as powerful as its ability to reach the patients who need it most. 

Contributors

Liat Vidal, MD | Senior Medical Director, Oncology