FDA Approves Teclistamab Combo for Relapsed/Refractory Multiple Myeloma
The Food and Drug Administration (FDA) has granted full approval to the combination of teclistamab-cqyv (Tecvayli, Johnson &. Johnson) and daratumumab hyaluronidase-fihj (Darzalex Faspro, Johnson & Johnson) for adults battling relapsed or refractory multiple myeloma, a cancer that affects plasma cells. This approval, granted on March 6, 2026, offers a latest treatment option for patients who have already undergone at least one prior line of therapy. The combination likewise received an upgrade to full traditional approval for teclistamab monotherapy in patients with relapsed or refractory multiple myeloma following at least four prior therapies.
MajesTEC-3 Trial Results Drive Approval
The FDA’s decision is based on data from the pivotal phase 3 MajesTEC-3 trial. This randomized study, involving 587 patients, demonstrated a significant reduction in the risk of disease progression or death for those receiving the teclistamab-daratumumab combination compared to standard care. Specifically, patients in the combination arm experienced an 83% reduction in risk for disease progression or death (HR = 0.17; 95% CI, 0.12 – 0.23). Median overall survival was also significantly improved (HR = 0.46; 95% CI, 0.32-0.65).
The MajesTEC-3 trial assigned patients to either the teclistamab-daratumumab combination (n = 291) or a control regimen consisting of daratumumab hyaluronidase-fihj with pomalidomide and dexamethasone, or daratumumab hyaluronidase-fihj with bortezomib and dexamethasone (n = 296). Strikingly, the 3-year progression-free survival (PFS) rate was 83.4% in the combination group, compared to just 29.7% in the control group. Similarly, the 3-year overall survival rate reached 83.3% with the combination, versus 65% in the control arm.
Understanding Multiple Myeloma and Treatment Approaches
Multiple myeloma is a cancer of plasma cells, a type of white blood cell responsible for producing antibodies. As myeloma cells accumulate in the bone marrow, they interfere with the production of healthy blood cells and can cause bone damage, anemia, kidney problems, and increased susceptibility to infection. Treatment options vary depending on the stage of the disease and the patient’s overall health, but often include chemotherapy, immunotherapy, stem cell transplantation, and targeted therapies. Relapsed or refractory multiple myeloma refers to cases where the cancer returns after initial treatment or does not respond to treatment in the first place.
Teclistamab is a bispecific antibody that targets both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T cells, effectively bringing the two together to enhance the immune system’s ability to kill cancer cells. Daratumumab is a monoclonal antibody that targets CD38, a protein found on the surface of myeloma cells, also triggering an immune response. Combining these two therapies aims to provide a more potent and sustained anti-myeloma effect.
Safety Considerations and Adverse Events
As with any cancer treatment, the teclistamab-daratumumab combination is associated with potential side effects. The most commonly reported adverse events in the MajesTEC-3 trial included hypogammaglobulinemia (low antibody levels), upper respiratory tract infection, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reactions, fatigue, fever, headache, nausea, gastroenteritis, and weight loss.
Serious adverse events occurred in 70.7% of patients treated with the combination, compared to 62.4% in the control group. Treatment was discontinued due to adverse events in 4.6% of patients in the combination arm and 5.5% in the control arm. Grade 5 treatment-emergent adverse events (death related to treatment) were slightly more frequent with the combination (7.1%) than with the control regimen (5.9%).
The prescribing information for teclistamab includes a boxed warning regarding the risk of life-threatening or fatal cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). These are serious immune-related complications that require careful monitoring and management.
Third Approval Under Priority Voucher Program
This approval marks the third instance of a treatment receiving FDA clearance under the Commissioner’s National Priority Voucher pilot program. This program is designed to incentivize the development of drugs for rare diseases and unmet medical needs. The voucher provides priority review for a subsequent FDA application, potentially accelerating the approval of another important therapy.
What In other words for Patients
“This new treatment option can redefine how we approach [relapsed or refractory multiple myeloma] treatment by giving health care providers a regimen with improvement in PFS and OS and a well-characterized safety profile,” said Luciano J. Costa, MD, professor of multiple myeloma and director of the multiple myeloma research and treatment program at the University of Alabama at Birmingham, in a Johnson & Johnson press release. Dr. Costa also highlighted the potential for earlier use of this regimen, even as a second-line treatment, given the tendency for multiple myeloma patients to experience multiple relapses and diminishing responses to therapy over time. He further noted the potential benefits of a steroid-sparing approach, which may reduce toxicity and improve tolerability.
The availability of this new combination therapy offers hope for patients with relapsed or refractory multiple myeloma, a challenging disease with limited treatment options. However, it’s crucial for patients to discuss the potential benefits and risks of this treatment with their healthcare providers to determine if it’s the right choice for their individual circumstances.
Looking Ahead: Ongoing Research and Monitoring
The FDA’s approval of teclistamab-daratumumab is a significant step forward in the treatment of multiple myeloma. Continued monitoring of long-term outcomes and further research are essential to fully understand the benefits and risks of this combination therapy. Researchers will also continue to explore new treatment strategies and combinations to improve the lives of patients with this challenging cancer. Patients and caregivers can stay informed about the latest developments by consulting with their healthcare teams and accessing reliable resources such as the National Cancer Institute and the Multiple Myeloma Research Foundation.