Johnson & Johnson has secured European Commission approval to use TECVAYLI, or teclistamab, together with daratumumab in adults with relapsed or refractory multiple myeloma after at least one previous therapy, significantly moving the bispecific antibody into earlier treatment. The approval is supported by the randomized Phase 3 MajesTEC-3 trial, where the combination reduced the risk of disease progression or death by 83.4% compared with established daratumumab-based regimens after nearly three years of follow-up. Overall survival also improved substantially, with 83.3% of patients receiving teclistamab plus daratumumab alive at three years compared with 65.0% in the control group.
The decision gives European physicians access to an off-the-shelf immunotherapy combination as early as second-line treatment, rather than reserving teclistamab for patients who have exhausted several previous therapies. That shift is clinically important because multiple myeloma repeatedly relapses, and successive remissions typically become shorter as patients move through later lines of treatment. The European Commission approval therefore moves a BCMA-directed bispecific antibody into a point in the disease course where patients generally retain better immune function and may have a greater opportunity to achieve prolonged disease control.
Phase 3 MajesTEC-3 results produced one of the strongest progression-free survival advantages in relapsed myeloma
MajesTEC-3 randomized 587 patients with relapsed or refractory multiple myeloma who had received one to three previous lines of therapy. A total of 291 patients received teclistamab plus subcutaneous daratumumab, while 296 received investigator-selected standard treatment consisting of subcutaneous daratumumab and dexamethasone combined with either pomalidomide or bortezomib. Progression-free survival was the primary endpoint, with complete response, overall response, minimal residual disease negativity, overall survival, symptom deterioration and safety included among the major secondary measures.
At nearly three years, the hazard ratio for progression or death was 0.17, corresponding to an 83.4% risk reduction compared with the control regimens. The result was highly statistically significant, while durability was particularly notable among patients who had already remained progression free for six months. More than 90% of those patients continued to remain progression free at three years, suggesting that early disease control with the combination could persist for a substantial period.
The survival result strengthens the clinical relevance of the progression-free survival finding. Teclistamab plus daratumumab reduced the risk of death by approximately 54%, with an overall survival hazard ratio of 0.46, and the survival advantage was reported across all prespecified patient subgroups. Three-year overall survival of 83.3% compared with 65.0% for standard treatment represents an 18.3 percentage-point absolute difference at that time point.
Response depth also strongly favored the immunotherapy doublet. At approximately three years of follow-up, 89% of patients receiving teclistamab plus daratumumab achieved an overall response compared with 75.3% on standard therapy. Complete response or better was achieved by 81.8% versus 32.1%, while minimal residual disease negativity reached 58.4% with the combination compared with 17.1% among control patients.
Those deeper responses matter because multiple myeloma can persist at levels too low to be detected through conventional response criteria. Minimal residual disease testing uses highly sensitive methods to search for remaining malignant plasma cells, and substantially higher MRD negativity suggests teclistamab plus daratumumab is capable of producing unusually deep suppression of the disease. The study also reported a longer period before worsening of patient-reported symptoms, adding evidence that the efficacy advantage was not restricted to laboratory and imaging measures.
Combining BCMA and CD38 targeting may explain why the immunotherapy doublet produced unusually durable disease control
TECVAYLI is a bispecific T-cell engager that simultaneously binds B-cell maturation antigen, or BCMA, on multiple myeloma cells and CD3 on T cells. By bringing T cells into close proximity with malignant plasma cells, teclistamab is designed to redirect the immune system toward killing the cancer. Unlike individualized cellular therapies, it is manufactured in advance and is therefore described as an off-the-shelf treatment.
Daratumumab attacks the disease through a separate target, CD38, which is highly expressed on multiple myeloma cells. Johnson & Johnson has said daratumumab also alters the immune environment in ways that can enhance T-cell fitness and activation, providing a biological rationale for combining it with teclistamab rather than simply administering two unrelated antimyeloma therapies together.
The European approval substantially broadens where teclistamab can be used. The European Commission initially authorized teclistamab in 2022 as monotherapy for adults with relapsed or refractory multiple myeloma who had received at least three previous therapies including an immunomodulatory drug, a proteasome inhibitor and an anti-CD38 antibody. The new indication allows the teclistamab-daratumumab combination after only one prior treatment, bringing the bispecific strategy much closer to the beginning of the relapse setting.
The change could influence treatment sequencing as clinicians decide whether to deploy powerful immune-directed therapies earlier instead of reserving them for heavily pretreated disease. Johnson & Johnson reported that more than 30,700 patients worldwide had received teclistamab by June 2026, while daratumumab has been used in more than 830,000 patients globally, providing physicians with extensive experience managing the individual components even though the combination represents a newer treatment strategy.
Infection risk remains a central consideration despite the strong survival advantage
The magnitude of the efficacy result has to be considered alongside an intensive safety profile. Grade 3 or Grade 4 treatment-emergent adverse events occurred in 95.1% of patients receiving teclistamab plus daratumumab and 96.6% of patients receiving the comparator regimens. Cytopenias and infections accounted for most of the severe events in both treatment groups.
Infections were particularly frequent with the bispecific combination. Any-grade infections occurred in 96.5% of patients receiving teclistamab plus daratumumab compared with 84.1% in the control group, while Grade 3 or Grade 4 infections occurred in 54.1% versus 43.4%, respectively. Johnson & Johnson reported that severe infections declined after the first six months as patients received immunoglobulin supplementation, infection prophylaxis and transitioned to monthly dosing.
Cytokine release syndrome occurred in 60.1% of patients receiving the teclistamab combination, although all events were Grade 1 or Grade 2 and none caused treatment discontinuation. Immune effector cell-associated neurotoxicity syndrome was uncommon at 1.1%, while treatment discontinuation because of treatment-emergent adverse events remained relatively low and similar between the groups at 4.6% for teclistamab and 5.5% for the comparator regimens.
These findings mean the combination should not be viewed simply as a more effective version of standard treatment without added management requirements. Infection prevention, immunoglobulin monitoring and management of immune-related complications remain important components of treatment, particularly during the earlier months when immune suppression can be most pronounced. The unusually large progression-free and overall survival advantages nevertheless provide physicians with a strong efficacy argument when weighing those risks.
European approval extends a combination already cleared in the United States and strengthens TECVAYLI’s second-line position
The European Commission decision follows United States approval of TECVAYLI plus DARZALEX FASPRO in March 2026 for adults with relapsed or refractory multiple myeloma after at least one prior therapy that included a proteasome inhibitor and an immunomodulatory agent. That earlier FDA decision and the new European authorization increasingly establish the combination as a commercial treatment rather than merely a late-stage development program.
The European opportunity remains significant despite improvements in multiple myeloma survival. More than 35,000 people were estimated to have been diagnosed with the disease across the European Union in 2024, while approximately 21,900 died. Multiple myeloma remains incurable for most patients, with repeated relapse creating continued demand for treatments capable of generating deeper and longer remissions.
The approval also reinforces Johnson & Johnson’s effort to build a treatment portfolio capable of covering different forms of relapse rather than relying on one therapeutic approach. Teclistamab has also produced positive Phase 3 monotherapy results in MajesTEC-9 among patients predominantly refractory to anti-CD38 therapy and lenalidomide, giving the company another potential route for positioning the BCMA bispecific earlier in the treatment sequence.
For clinicians, the most striking feature of MajesTEC-3 is not simply that another multiple myeloma combination achieved approval. An 83.4% reduction in progression or death, an 18-point advantage in three-year overall survival and complete responses in more than four-fifths of treated patients collectively set a demanding benchmark for therapies competing in the early relapse setting. The remaining practical question is how widely that efficacy can be reproduced outside clinical trials while physicians manage the higher infection burden associated with intensive immune-directed treatment.
Johnson & Johnson shares entered August 21 after a strong year, with the stock reported to have gained roughly 30.5% during 2026 even after declining during the previous session. The European Commission approval is supportive of the Innovative Medicine portfolio, although a company of Johnson & Johnson’s size is driven by numerous pharmaceutical, medical technology, legal and macroeconomic factors, making it inappropriate to attribute the broader stock performance primarily to TECVAYLI.
The approval nevertheless adds another meaningful regulatory expansion to a franchise already generating growing clinical adoption. The more important strategic implication is that bispecific antibodies are moving rapidly from heavily pretreated multiple myeloma into earlier relapse, where larger patient populations and longer treatment durations could substantially increase their clinical and commercial importance.
