FDA Approves Teclistamab Plus Daratumumab for Relapsed/Refractory Multiple Myeloma

On March 5, the FDA approved teclistamab-cqyv (Tecvayli) in combination with daratumumab and hyaluronidase-fihj (Darzelex Faspro) for adults with relapsed or refractory multiple myeloma.¹ The approval is supported by Phase III data from the MajesTEC-3 study and carries Breakthrough Therapy Designation, signaling both the strength of the clinical evidence and the unmet need in this population.

The approval represents the first regulatory conversion of a bispecific T-cell engager from accelerated to full approval based on randomized Phase III survival data in multiple myeloma.¹ This new combination strategy, a CD3/B-cell maturation antigen bispecific paired with a CD38-directed antibody, works synergistically to prime and activate the immune system against myeloma cells. The regimen is also subcutaneously administered, a formulation consideration with growing relevance across the field.

What Are the Phase III Trial Results?

The MajesTEC-3 study compared teclistamab plus daratumumab against investigators' choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in patients with relapsed or refractory multiple myeloma who had received at least one prior line of therapy. After a median follow-up of three years, the combination demonstrated an 83% reduction in the risk of disease progression or death compared to standard regimens. The three-year progression-free survival rate was 83% in the combination arm versus 30% in the control arm (Figure 1).

"This new treatment option can redefine how we approach relapsed/refractory multiple myeloma treatment by giving healthcare providers a regimen with improvement in progression-free survival and overall survival and a well-characterized safety profile," said Dr. Luciano J. Costa, professor of multiple myeloma and director of the Multiple Myeloma Research and Treatment Program, University of Alabama at Birmingham, and Primary Investigator of MajesTEC-3, in a press release.¹ "The option to use this regimen as early as second line is particularly important because patients with relapsed/refractory multiple myeloma often experience multiple relapses and reduced responsiveness to therapy over time, which makes earlier treatment with the most effective therapies critical. In addition, the steroid-sparing approach may reduce toxicity and improve tolerability."

Overall survival also favored the combination, with three-year overall survival rates of 83.3% versus 65.0% in the control arm, a meaningful separation that held across all prespecified subgroups (Figure 1).¹ The combination also showed higher rates of overall response, 89.0% versus 75.3%. The complete response is better, 81.8% versus 32.1%. There was minimal residual disease negativity, 58.4% versus 17.1%, at three-year follow-up.

Figure 1: Comparing Overall Results

How Does the Safety Profile Shape the Clinical and Manufacturing Picture?

The safety data from MajesTEC-3 are relevant to both clinical teams and those involved in the development of comparable modalities.¹ Rates of Grade 3/4 treatment-emergent adverse events were similar across arms (Figure 2) with most events attributable to cytopenias and infection. Cytokine release syndrome occurred in 60.1% of patients receiving the combination, though all cases were Grade 1 or 2, did not lead to treatment discontinuation, and were managed using standard guidelines. Immune effector cell-associated neurotoxicity syndrome was rare at 1.1%. Notably, Grade 3 or higher infections declined after the first six months of treatment, consistent with the use of immunoglobulin supplementation, infection prophylaxis protocols, and a switch to monthly dosing—a pattern that has implications for real-world administration planning. Treatment discontinuations due to adverse events were low, at 4.6% in the combination arm versus 5.5% in the control arm.

Figure 2: Comparing Safety Profiles

"There is a critical need to expand community-based treatment options for multiple myeloma patients, allowing them to receive care closer to home while respecting their individual treatment preferences," stated Heather Ortner Cooper, president and CEO, International Myeloma Foundation, in a press release.¹ "This approval enhances the therapeutic landscape, giving oncologists diverse options to personalise treatment plans for each patient."

The approval makes teclistamab the first bispecific antibody in multiple myeloma to convert from accelerated to full approval on the basis of a confirmatory randomized Phase III trial.¹ The FDA also selected the supplemental biologics license application for participation in the commissioner's national priority voucher pilot program, and granted real-time oncology review, reflecting the agency's prioritization of the submission.

For the approximately 40% of patients with multiple myeloma who experience disease relapse, and for the more than 35,000 people estimated to be newly diagnosed in the US annually, the earlier availability of this regimen represents a material shift in the therapeutic options that oncologists can offer.

How Else is J&J Evolving Its Production Portfolio?

Beyond multiple myeloma, Johnson & Johnson is advancing its pipeline in autoimmune disease through nipocalimab, an investigational therapy that selectively lowers harmful immunoglobulin G antibodies, while preserving broader immune function.² The FDA granted nipocalimab fast track designation in systemic lupus erythematosus in January 2026, its fifth such designation across different indications. This followed positive Phase II data in which nipocalimab reduced lupus disease activity and demonstrated steroid-sparing potential. A Phase III study in adults with active systemic lupus erythematosus is currently enrolling, with the company also investigating nipocalimab across rare and maternal-fetal autoantibody diseases.

References

1. Johnson & Johnson. Johnson & Johnson announces U.S. FDA approval of TECVAYLI plus DARZALEX FASPRO for relapsed/refractory multiple myeloma, offering a potential new standard of care as early as second line. News release. March 4, 2026. Accessed March 6, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-u-s-fda-approval-of-tecvayli-plus-darzalex-faspro-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care-as-early-as-second-line
2. Johnson & Johnson. Johnson & Johnson therapy nipocalimab granted U.S. FDA Fast Track designation in systemic lupus erythematosus (SLE). News release. March 3, 2026. Accessed March 6, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-therapy-nipocalimab-granted-u-s-fda-fast-track-designation-in-systemic-lupus-erythematosus-sle