J&J wins EC approval for teclistamab plus daratumumab in RRMM

Johnson & Johnson has secured a European Commission indication extension for teclistamab (TECVAYLI) in combination with daratumumab, covering adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy. The decision moves the BCMAxCD3 bispecific antibody into earlier lines of treatment than its original 2022 authorisation, which was limited to patients with at least three prior therapies.

The approval rests on data from the Phase 3 MajesTEC-3 study (NCT05083169), published in the New England Journal of Medicine in 2025, which compared the combination against investigator's choice of daratumumab plus dexamethasone with either pomalidomide or bortezomib in patients with one to three prior lines of therapy.

The MajesTEC-3 data

The trial results are striking by the standards of the RRMM field. At nearly three years of follow-up, teclistamab plus daratumumab reduced the risk of disease progression or death by 83.4% relative to standard-of-care comparators, with a hazard ratio of 0.17 (95% CI, 0.12 to 0.23; p less than 0.001). More than 90% of patients who remained progression-free at six months were still progression-free at the three-year mark, suggesting a durable plateau rather than the usual pattern of gradual attrition. Overall survival also favoured the combination, with a hazard ratio of 0.46 (95% CI, 0.32 to 0.65; p less than 0.0001); at three years, OS rates were 83.3% for the doublet versus 65.0% for the comparator arms.

The safety profile was described as consistent with the known profiles of each agent individually. All cytokine release syndrome events were Grade 1 or 2 and did not lead to treatment discontinuation. Grade 3 or 4 cytopenias and infections were the most common serious adverse events, and treatment discontinuation due to adverse events was low in both arms, at 4.6% for the combination versus 5.5% for the comparators.

María-Victoria Mateos, Director of the Myeloma Unit at the University Hospital of Salamanca, said the approval provides "an off-the-shelf, steroid-sparing, immunotherapy option that has demonstrated meaningful improvements in progression-free and overall survival, with the potential to redefine treatment expectations as early as second line."

Market context and competitive landscape

The RRMM space has undergone rapid transformation over the past three years, with bispecific antibodies and CAR-T cell therapies both competing to push into earlier lines of treatment. Teclistamab's approval in 2022 as a later-line monotherapy was followed by the entry of other BCMA-directed agents, including elranatamab from Pfizer and ide-cel and cilta-cel as CAR-T options, which carry more complex logistics owing to their autologous manufacturing requirements.

The combination with daratumumab is significant because daratumumab is already embedded as a backbone therapy across multiple myeloma, giving clinicians a familiar partner drug rather than a novel triplet. The off-the-shelf, subcutaneous delivery of both components addresses one of the practical barriers associated with cell therapies and positions the doublet as viable for community oncology settings as well as academic centres. More than 830,000 patients have received daratumumab worldwide since its launch, and teclistamab has now been administered to more than 30,700 patients globally.

From a regulatory standpoint, the EC approval follows presentation of MajesTEC-3 data at the American Society of Hematology annual meeting in December 2025 and aligns with MHRA and EMA interest in approving novel immunotherapy combinations earlier in the treatment sequence, where survival benefit can be maximised. Johnson & Johnson is continuing to investigate teclistamab in further combination studies, including with talquetamab, its GPRC5DxCD3 bispecific, suggesting the company intends to build out a broader myeloma franchise built on T-cell redirecting backbones.

In the EU, more than 35,000 new myeloma diagnoses were recorded in 2024, representing a substantial and growing patient population as the disease skews toward older age groups.