Immunotherapy Combination Teclistamab Plus Daratumumab Lowers Risk of Death for People with Relapsed/Refractory Multiple Myeloma

Despite recent advances in multiple myeloma treatment, when myeloma comes back (relapses) or progresses during treatment (refractory), it can be difficult to control with available medications. People with relapsed/refractory myeloma often have worse results after each treatment, and there remains a need for more effective, long-lasting therapies for these patients. 

A combination immunotherapy treatment of teclistamab (Tecvayli, Janssen Biotech) and daratumumab (Darzalex Faspro, Janssen Biotech) showed unprecedented results that were described as “clinically remarkable” in treating relapsed/refractory multiple myeloma. When compared to the current standard of care, teclistamab and daratumumab had a 54% lower risk of death. The results were presented at the American Society of Hematology (ASH) Annual Meeting.

“The combination of teclistamab and daratumumab subcutaneous (SC) offers remarkable efficacy and safety consistent with their known profiles, and, alongside robust infection management protocols, an opportunity to improve patient outcomes across academic and community settings. It has the potential to change the standard of care as a steroid-sparing combination regimen suited for outpatient administration on the familiar daratumumab SC schedule,” said María-Victoria Mateos, M.D., Ph.D. of the University Hospital of Salamanca.

Understanding the phase 3 MajesTEC-3 clinical trial 

The phase 3 MajesTEC-3 clinical trial tested the immunotherapy combination of teclistamab and daratumumab (Tec-Dara) for relapsed/refractory myeloma patients who have received one or more lines of therapy. The new combination was compared to the standard of care: 

• DPd, which is daratumumab, pomalidomide (Pomalyst), and dexamethasone

• DVd, which is daratumumab, bortezomib (Velcade), and dexamethasone

There were 587 patients enrolled in the study. They were randomly assigned to receive either Tec-Dara (291 patients) or DPd/DVd (296 patients). Patients in the DPd/DVd group could have received either treatment.

To be eligible for the trial, people had to have one to three prior lines of therapy that included a proteasome inhibitor and lenalidomide. If they only had one prior line of therapy, they needed to have disease progression while being treated with lenalidomide. The median age was 64, and the median number of prior lines of treatment was two. 

What were the results of the MajesTEC-3 clinical trial?

Tec-Dara significantly improved progression-free survival (PFS) compared to DPd/DVd. PFS is the amount of time after treatment begins when cancer does not progress. After 2.8 years, the median PFS for the Tec-Dara group had not yet been reached. This means that more than half of patients had not had their cancer progress at the time of the follow-up. The median PFS in the DPd/DVd group was 18.1 months. At 2.8 years, 83.4% of patients had not had their cancer progress in the Tec-Dara group compared to 29.7% in the DPd/DVd group. The improved progression-free survival rate was seen across all subgroups in the study, including adults aged 75 and above and those with high-risk cytogenetics. 

There were significantly higher rates of complete response (CR) in the tec-dara group (81.8%) compared to the DPd/DVd group (32.1%). The Tec-Dara group also had a better MRD-negativity rate (58.4%) compared to the DPd/DVd group (17.1%). MRD negativity means no myeloma cells are found in the bone marrow.

Finally, the overall survival (OS) rates were significantly higher in the Tec-Dara group. At 2.8 years, 83.3% of patients treated with Tec-Dara were still alive, compared to 65% of patients treated with DPd/DVd. Patients treated with Tec-Dara were 54% less likely to die than patients treated with DPd/DVd. More than 90% of the patients treated with Tec-Dara who were alive after 6 months of treatment were still alive at 30 months. 

Side effects of teclistamab and daratumumab

Severe side effects occurred at similar rates across both treatment groups. The most common side effect in both groups was neutropenia. Neutropenia is a low count of a type of white blood cell called neutrophils. There were slightly more serious side effects in the Tec-Dara group (70.7% vs. 62.4%). In both groups, few participants stopped treatment because of side effects.

There was a higher rate of infections in the Tec-Dara group, with 96.5% of patients developing an infection compared to 84.1% of the DPd/DVd group. The rates of new, severe infections decreased over time. About 60% of patients in the Tec-Dara group experienced cytokine release syndrome (CRS) and 1.1% ICANS, but they were mild. 

These results show that teclistamab and daratumumab is a highly effective combination that is widely available in a community setting.

How do teclistamab and daratumumab treat relapsed/refractory multiple myeloma?

Teclistamab is a BCMA-targeting bispecific antibody. It recognizes the B-cell maturation antigen, which is a protein found on myeloma cells. It is already approved to treat relapsed/refractory multiple myeloma patients who have received at least four prior lines of therapy.

Daratumumab is an anti-CD38-targeting monoclonal antibody. It enhances the immune system by both stopping immunosuppressing T-cells and expanding T-cells that attack myeloma cells. It is a widely prescribed medication for both newly diagnosed and relapsed/refractory myeloma. 

Together, these immunotherapy medications activate the body’s own immune system to find and destroy myeloma cells.

When given as part of this combination, both teclistamab and daratumumab are a subcutaneous injection. Subcutaneous means under the skin.

Is dexamethasone needed when treated with teclistamab and daratumumab?

Dexamethasone, a steroid, is required for the first eight days of treatment with teclistamab and daratumumab, but it is not given with this combination after that. This is important because dexamethasone can have challenging side effects. This treatment regimen allows patients to avoid dexamethasone. 

What does this mean for patients?

For people with relapsed/refractory multiple myeloma, a treatment combination of teclistamab and daratumumab could be an effective second-line or later treatment option. Finding new ways of using effective therapies can expand options for people who have tried more than one lines of treatment. 

The latest myeloma research, delivered to your inbox

Stay up-to-date with the latest myeloma research outcomes, HealthTree programs, and community events by subscribing to the HealthTree newsletter today.

Subscribe Today