Teclistamab Combo Earns EU Approval in Relapsed/Refractory Multiple Myeloma

The European Commission (EC) has approved an indication extension for teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex) for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 1 prior therapy, according to a news release from Johnson & Johnson.¹ The approval introduces the immunotherapy doublet as a treatment option as early as the second line; it is supported by data from the phase 3 MajesTEC-3 trial (NCT05083169), which evaluated the regimen against investigator’s choice of standard-of-care combinations.

What MajesTEC-3 data supported the approval?

At nearly 3 years of follow-up, teclistamab plus subcutaneous daratumumab reduced the risk of disease progression or death by 83.4% compared with standard of care (HR, 0.17; 95% CI, 0.12-0.23; P <.001). More than 90% of patients who remained progression-free at 6 months (n = 249) were still progression free at 3 years. Overall survival (OS) data favored the experimental regimen (HR, 0.46; 95% CI, 0.32-0.65; P <.0001), with benefit observed across all prespecified subgroups. At 3 years, the OS rate was 83.3% with teclistamab plus daratumumab vs 65.0% with standard of care.

“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. 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 [PFS] and [OS],” said María-Victoria Mateos, MD, PhD, director of the Myeloma Unit at the University Hospital of Salamanca in Spain, in the press release.¹

What was the safety profile?

The safety profile of teclistamab plus subcutaneous daratumumab was consistent with the established profiles of the individual agents, with no new safety signals identified. All cases of cytokine release syndrome were grade 1 or 2 and did not lead to treatment discontinuation. Cytopenia and infection were the most common grade 3/4 treatment-emergent adverse events (TEAEs). Treatment discontinuations due to TEAEs were low and occurred at similar rates between arms, at 4.6% with teclistamab vs 5.5% with the comparator.

What was the MajesTEC-3 trial design?

MajesTEC-3 is an ongoing, phase 3 randomized study evaluating teclistamab plus subcutaneous daratumumab (n = 291) vs investigator’s choice of subcutaneous daratumumab and dexamethasone with either pomalidomide (Pomalyst; DPd) or bortezomib (Velcade; DVd; n = 296) in patients with relapsed/refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

The primary end point is PFS. Secondary end points include complete response or better, overall response rate, minimal residual disease negativity, OS, time to worsening of symptoms, and safety.

What is teclistamab’s regulatory history in multiple myeloma?

Teclistamab is an off-the-shelf, BCMA/CD3 bispecific antibody that first received EC approval in August 2022 for patients with relapsed/refractory multiple myeloma who had received at least 3 prior therapies.² Previously, the European Medicines Agency’s Committee for Medicinal Products for Human Use issued a positive opinion recommending the teclistamab/daratumumab indication extension in June 2026.³ Furthermore, the FDA approved teclistamab/daratumumab for those with relapsed/refractory multiple myeloma after at least 1 prior line of therapy in March 2026.⁴

Daratumumab is a CD38-directed antibody that modulates the immune system and enhances T-cell activity, complementing teclistamab’s redirection of T cells against myeloma cells.

“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,” Ester in ‘t Groen, the Europe, the Middle East, and Africa Therapeutic Area Head of Haematology at Johnson & Johnson, concluded.¹

References

1. European Commission approves Johnson & Johnson’s Tecvayli (teclistamab) plus daratumumab for relapsed/refractory multiple myeloma, offering a potential new standard of care. News release. Johnson & Johnson. August 21, 2026. Accessed August 24, 2026. https://tinyurl.com/28t44sdn
2. Janssen marks first approval worldwide for TECVAYLI® (teclistamab) with EC authorisation of first-in-class bispecific antibody for the treatment of patients with multiple myeloma. News release. Jansen. August 24, 2022. Accessed August 24, 2026. https://bit.ly/3wsRYFP
3. CHMP recommendation advances Johnson & Johnson’s Tecvayli (teclistamab) plus daratumumab as a potential standard of care for relapsed/refractory multiple myeloma. News release. Johnson & Johnson. June 26, 2026. Accessed August 24, 2026. https://tinyurl.com/mt4mc5k7
4. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed August 24, 2026. https://tinyurl.com/45hhbpau