Researchers have made great progress in the treatment of multiple myeloma, a rare blood cancer, over the past decade. One important advance has been the emergence of a new class of drugs called bispecific antibodies, which work well in people for whom previous treatments have failed.
Now new results from a clinical trial show that giving two bispecific antibodies in combination can be effective in people with extramedullary myeloma, an especially resistant form of multiple myeloma. When given together, the drugs, teclistamab and talquetamab, delayed progression of the disease nearly three times longer than current therapies for these high-risk patients. Most patients also survived more than twice as long.
“These are impressive results, showing that combination therapy could be a big step forward for people with extramedullary myeloma, who urgently need better treatments,” says Memorial Sloan Kettering Cancer Center (MSK) hematologic oncologist Saad Usmani, MD.
Dr. Usmani, Chief of MSK’s Myeloma Service, helped lead the combination therapy trial and is presenting the results at the 2025 American Society of Hematology Annual Meeting (ASH). The study is being simultaneously published in the New England Journal of Medicine.
Dr. Usmani has more than 15 years of experience specializing in the care of patients with multiple myeloma and other disorders affecting plasma cells. Previously, he led the way in shepherding teclistamab through the clinical testing from its earliest stage, which led the U.S. Food and Drug Administration (FDA) to approve the drug for multiple myeloma in 2022. He also led the first efforts to describe and characterize extramedullary myeloma as a specific type of the disease in 2012.
What Are the Types and Symptoms of Multiple Myelomas?
Multiple myeloma arises from a type of white blood cell called a plasma cell and develops when it changes into a myeloma cell, which can multiply uncontrollably. Multiple myeloma symptoms include bone pain or fractures, backache, frequent infections, weight loss, fatigue, and other conditions.
Many multiple myeloma patients today can live well for years, but certain types of the disease can be very difficult to treat.
Extramedullary myeloma is an aggressive form of the disease that develops when multiple myeloma cells form tumors outside the bone marrow, in organs or soft tissues. When extramedullary myeloma relapses, the prognosis is very poor, with median survival at around five months.
How Do Bispecific Antibodies Work?
Bispecific antibodies are engineered to target two proteins at once, bringing different cells — such as cancer cells and immune T cells — close together. This enables the immune system to target and destroy cancer cells more effectively.
Teclistamab and talquetamab both target a protein on T cells called CD3, but each binds to different proteins on myeloma cells. Teclistamab targets a protein called BCMA, while talquetamab binds to a protein called GPRC5D.
Clinical Trial Results for Extramedullary Myeloma Treatment
The phase 2 clinical trial involved extramedullary myeloma patients whose disease was either resistant or had returned despite previous treatment with at least one drug from each of the three main classes of standard therapy.
Among 90 patients who received the combination therapy, 78.9% achieved a response at some point. Median progression-free survival with the combination treatment was 15.4 months, compared with less than 3 months in people receiving standard therapy and less than 6 months in people receiving just one of the bispecific antibodies.
The therapy’s effect also appeared to be lasting. After one year:
- 64.1% of patients were still responding.
- 61% had progression-free survival.
- 74.5% were still alive, compared with a median overall survival of 5 months under standard treatment.
- While most patients had side effects, they were manageable.
Dr. Usmani says these results suggest the combination treatment works better than other therapies that have been used for these high-risk patients. This includes drugs such as targeted therapies and monoclonal antibodies, as well as a newer type of treatment called CAR T cell therapies, which genetically engineer a patient’s own immune cells.
“Combining teclistamab and talquetamab appears to work much better than either drug by itself,” Dr. Usmani says. “This new class of drugs has already shown enormous potential for all forms of multiple myeloma, and now we see that combining them can have major advantages.”
Key Takeaways
- Multiple myeloma patients today can live well for years, but certain types of the disease can be very difficult to treat.
- Extramedullary myeloma is an aggressive form of the disease with median survival at around five months.
- A new treatment combining two drugs dramatically delayed progression of the disease and improved survival.
- The drugs, teclistamab and talquetamab, are engineered to target two proteins at once.
