People with multiple myeloma often respond well to their first treatment, but the disease usually returns over time. Each relapse can become more difficult to treat, making new therapies an important area of research.
A new Phase 3 clinical trial published in the New England Journal of Medicine found that talquetamab-based treatment combinations significantly improved progression-free survival and produced deeper responses than a commonly used standard therapy in patients with relapsed or refractory multiple myeloma. The study evaluated both a two-drug regimen (talquetamab plus daratumumab) and a three-drug regimen (talquetamab, daratumumab, and pomalidomide), with both combinations demonstrating substantial clinical benefit.
What Is Multiple Myeloma?
Multiple myeloma is a cancer of plasma cells, a type of white blood cell that helps the body fight infection by producing antibodies.
In people with multiple myeloma, abnormal plasma cells build up in the bone marrow and crowd out healthy blood cells. This can lead to symptoms such as bone pain or fractures, fatigue, frequent infections, kidney problems, and high calcium levels.
Although many patients initially respond to treatment, multiple myeloma is considered a chronic disease, and most people will eventually experience a relapse. When the disease returns after treatment, it is called relapsed multiple myeloma. If it no longer responds to treatment, it is considered refractory.
How Do These Treatments Work?
The study focused on talquetamab, a type of immunotherapy known as a bispecific antibody. It is designed to bring the body’s T cells, which help fight disease, into direct contact with multiple myeloma cells, allowing the immune system to better recognize and destroy the cancer.
Researchers combined talquetamab with one or two established myeloma treatments:
- Daratumumab, a monoclonal antibody that targets the CD38 protein found on myeloma cells.
- Pomalidomide, an immunomodulatory drug that helps stimulate the immune system while also slowing the growth of myeloma cells.
Because these medicines attack the cancer in different ways, researchers wanted to determine whether combining them could improve patient outcomes compared with current standard treatment.
How Was the Study Conducted?
The international Phase 3 MonumenTAL-3 trial enrolled 864 adults with relapsed or refractory multiple myeloma who had received at least one previous line of therapy. Participants were randomly assigned to receive one of three treatment regimens:
- Talquetamab, daratumumab, and pomalidomide (Tal-DP)
- Talquetamab and daratumumab (Tal-D)
- Daratumumab, pomalidomide, and dexamethasone (DPd), a commonly used standard treatment
The primary goal of the study was to measure progression-free survival, or how long patients lived before their cancer worsened. Researchers also evaluated response rates, complete responses, measurable residual disease (MRD), overall survival, and safety.
What Did the Study Find?
Both talquetamab-based combinations significantly outperformed the standard treatment. After 24 months, 81.3% of patients receiving Tal-DP remained alive without their disease progressing. 77.6% of patients receiving Tal-D remained progression-free, while 51.2% of patients receiving the standard DPd regimen had not experienced disease progression. Compared with the standard treatment, the three-drug combination reduced the risk of disease progression or death by 72%, and the two-drug combination reduced the risk by 67%.
The talquetamab-based regimens also produced deeper responses. Nearly 89% of patients receiving either talquetamab combination experienced a measurable response to treatment, compared with 78% of those receiving the standard regimen. Patients treated with talquetamab were also about twice as likely to achieve a complete response, meaning no signs of cancer could be detected using standard testing.
Researchers also measured minimal (or measurable) residual disease (MRD), which refers to the small number of cancer cells that can remain after treatment and eventually lead to relapse. Patients receiving talquetamab were much more likely to become MRD-negative, meaning highly sensitive tests could no longer detect remaining myeloma cells. Although MRD negativity does not guarantee a cure, it is generally associated with better long-term outcomes.
The side effects observed in the study were generally consistent with what has been seen in previous studies of talquetamab and other myeloma therapies.
What Does This Mean for Patients?
The results of the MonumenTAL-3 trial suggest that talquetamab-based combinations may become an important new treatment option for people with relapsed or refractory multiple myeloma.
Both the two-drug regimen of talquetamab plus daratumumab and the three-drug regimen that also included pomalidomide significantly delayed disease progression and produced deeper responses than a commonly used standard treatment.
One particularly encouraging finding was that the two-drug combination performed nearly as well as the three-drug regimen, raising the possibility that some patients may achieve excellent outcomes with fewer medications. Additional follow-up will help determine whether these benefits translate into longer overall survival and which patients are most likely to benefit from each approach.
As researchers continue to develop new immunotherapies, studies like MonumenTAL-3 are helping expand treatment options and improve outcomes for people living with multiple myeloma.
Questions to Ask Your Doctor
If you have relapsed or refractory multiple myeloma, you may want to ask your healthcare team:
- Am I a candidate for a talquetamab-based treatment?
- Would a two-drug or three-drug regimen be more appropriate for me?
- What side effects should I expect?
- How will my response to treatment be monitored?
- Is this treatment available to me, or is it still being studied?
Reference
Mina R, Beksac M, Rodríguez-Otero P, et al. Talquetamab–Daratumumab in Relapsed or Refractory Myeloma. New England Journal of Medicine. Published July 23, 2026. doi:10.1056/NEJMoa2604657.
