European Commission (EC) has approved an indication extension for teclistamab in combination with daratumumab for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy. The approval introduces a new treatment option as early as second line for patients living with RRMM.

Complementary mechanisms of action underpin this immunotherapy doublet

Teclistamab and daratumumab work in a complementary manner, with daratumumab modulating the immune system to enhance T-cell fitness and activation, thereby amplifying teclistamab-mediated killing of myeloma cells.

Expert and company perspectives on advancing the standard of care in RRMM

“Patients with relapsed or refractory multiple myeloma often experience shorter remissions and diminishing responses with each subsequent line of therapy, making earlier access to the most effective treatments increasingly important,” said María-Victoria Mateos, M.D., Director of the Myeloma Unit at the University Hospital of Salamanca, Spain. “Today’s approval of teclistamab in combination with daratumumab marks an important advance by providing physicians with 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.”

"This new indication for teclistamab plus daratumumab brings forward a new standard of care for patients in Europe living with relapsed or refractory multiple myeloma," said Ester in 't Groen, EMEA Therapeutic Area Head, Haematology, Johnson & Johnson. "By combining the complementary mechanisms of teclistamab, a BCMAxCD3 bispecific antibody, with daratumumab, a well-established standard of care that helps modulate the immune system, we can deliver meaningful long-term outcomes earlier in the treatment journey, where they have the greatest opportunity to influence the disease trajectory and redefine expectations for patients.”

“Today’s approval reflects our ongoing commitment to addressing the diverse needs of patients with multiple myeloma, giving them more options at every stage of their disease,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “By continuing to invest in scientific innovation and practice-changing research, we aim to redefine what is possible for patients today, while moving closer to a future where long-term disease control, and ultimately cure, becomes an achievable goal."

Unprecedented Phase 3 study data demonstrate significant survival benefits versus standard of care, representing a potential new benchmark in RRMM

The EC approval is supported by data from the Phase 3 MajesTEC-3 study (NCT05083169), which evaluated the efficacy and safety of teclistamab plus daratumumab subcutaneous (SC) formulation versus investigator’s choice of daratumumab SC and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with RRMM who have received 1–3 prior lines of therapy.

Source: Costa L, et al. Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma. The New England Journal of Medicine 2025; Full article and supplementary material. 

The study demonstrated clinically meaningful and statistically significant improvements in both progression-free survival (PFS) and overall survival (OS). At nearly three years of follow-up, teclistamab plus daratumumab SC reduced the risk of disease progression or death by 83.4% compared to standard of care (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.12-0.23; p<0.001). More than 90% of patients who remained progression-free at six months (n=249) remained progression-free at three years, highlighting the durability of response observed with this regimen. OS favoured teclistamab plus daratumumab SC (HR, 0.46; 95% CI, 0.32-0.65; p<0.0001), with treatment benefit observed across all prespecified subgroups. At three years, OS rates were 83.3% for the combination compared with 65.0% for standard of care.

Teclistamab combination demonstrated manageable safety profile

The safety profile of teclistamab plus daratumumab SC was consistent with the well-known profiles of the individual therapies and no new safety signals were identified. All cases of cytokine release syndrome were Grade 1/2 and did not lead to treatment discontinuation. Cytopenia and infection were the most commonly observed Grade 3/4 treatment-emergent adverse events (TEAEs). Treatment discontinuations due to TEAEs were low and occurred at similar rates between study arms (4.6% [teclistamab] vs. 5.5% [DPd/DVd]).

Source: Johnson & Johnson EMEA