European Commission Approves Teclistamab Plus Daratumumab for R/R Myeloma

The European Commission has approved teclistamab (Tecvayli) in combination with daratumumab (Darzalex) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy.¹

The approval was supported by data from the phase 3 MajesTEC-3 trial (NCT05083169). Data presented at the 2025 ASH Annual Meeting and Exposition showed that at a median follow-up of 34.5 months, patients treated with teclistamab plus daratumumab (n = 291) achieved a median progression-free survival (PFS) that was not reached compared with 18.1 months for those given investigator’s choice of daratumumab plus pomalidomide (Pomalyst) and dexamethasone (DPd) or daratumumab plus bortezomib (Velcade) and dexamethasone (DVd; n = 296; HR, 0.17; 95% CI, 0.12-0.23; P < .0001).² The respective 36-month PFS rates were 83.4% vs 29.7%. Overall survival (OS) also favored the teclistamab combination (HR, 0.46; 95% CI, 0.32-0.65; P < .0001), with 36-month OS rates of 83.3% vs 65.0%.

“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,” María-Victoria Mateos, MD, PhD, director of the Myeloma Unit at the University Hospital of Salamanca in Spain, stated in a news release.¹ “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.”

The European Union approval followed the March 2026 FDA approval of teclistamab-cqyv in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy.³

How was the MajesTEC-3 trial designed?

MajesTEC-3 was a randomized, open-label, phase 3 study that enrolled 587 patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and lenalidomide (Revlimid).²

Patients who had received only 1 prior line were required to be refractory to lenalidomide according to International Myeloma Working Group criteria, and an ECOG performance status of 0 to 2 was required. Patients were excluded if they had received prior BCMA-directed therapy or were refractory to anti-CD38 monoclonal antibodies.

Patients were randomly assigned 1:1 to receive teclistamab plus daratumumab (n = 291) or investigator’s choice of DPd or DVd (n = 296), of whom 91% received DPd. In the experimental arm, both agents were administered subcutaneously on a schedule aligned with the approved daratumumab regimen, with dexamethasone limited to premedication and no longer required after cycle 1 day 8. The median number of prior lines of therapy was 2, and more than 85% of patients were refractory to an immunomodulatory drug.

PFS per independent review committee assessment served as the primary end point. Secondary end points included complete response (CR) or better rate, overall response rate (ORR), minimal residual disease (MRD)–negativity rate, OS, time to worsening of symptoms, and safety.

What did additional efficacy and safety data show?

The ORR was 89.0% with teclistamab plus daratumumab compared with 75.3% with DPd or DVd (odds ratio [OR], 2.65; 95% CI, 1.68-4.18; P < .0001), and CR or better rates were 81.8% vs 32.1%, respectively (OR, 9.56; 95% CI, 6.47-14.14; P < .0001).

MRD-negativity rates at a sensitivity of 10⁻⁵ were 58.4% with the combination vs 17.1% with the control regimens (OR, 6.78; P < .0001). The median duration of response (DOR) was not estimable with teclistamab plus daratumumab vs 23.5 months with DPd or DVd, and the 36-month DOR rates were 88.5% vs 36.4%.

The safety profile of teclistamab plus daratumumab was consistent with the known profiles of the individual agents, and no new safety signals were identified. Grade 3 or 4 treatment-emergent adverse effects (TEAEs) occurred in 95.1% of patients receiving the combination vs 96.6% of those in the control arm; the most common hematologic TEAEs in the experimental arm were neutropenia (78.4%), anemia (39.2%), and thrombocytopenia (36.4%). TEAEs led to treatment discontinuation in 4.6% and 5.5% of patients, respectively; serious AEs occurred at respective rates of 70.7% vs 62.4%, and TEAEs led to death in 7.1% vs 5.9% of patients, respectively.

Cytokine release syndrome (CRS) occurred in 60.1% of patients treated with the teclistamab combination and was limited to grade 1 (44.2%) and grade 2 (15.9%), with no grade 3 or higher CRS reported. All CRS events resolved, and no grade 2 or higher events occurred after the first cycle, with no prophylactic tocilizumab was administered per protocol. Immune effector cell–associated neurotoxicity syndrome was reported in 1.1% of patients and resolved in all cases. Infections were common, occurring in 96.5% of patients in the combination arm; grade 3 or higher infections were highest during the first 6 months of treatment and declined thereafter. Hypogammaglobulinemia was reported in 84.5% of patients, and 13 patients (4.6%) died of infection, prompting a February 2023 protocol amendment to reinforce immunoglobulin replacement therapy and antimicrobial prophylaxis.

“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, EMEA therapeutic area head, hematology, at Johnson & Johnson, stated in a news release.¹ “By combining the complementary mechanisms of teclistamab, a BCMA x CD3 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.”

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 19, 2026. Accessed August 21, 2026. https://www.jnj.com/innovativemedicine/emea/media-center/press-releases/european-commission-approves-johnson-johnsons-tecvayli-teclistamab-plus-daratumumab-for-relapsed-refractory-multiple-myeloma-offering-a-potential-new-standard-of-care
2. Mateos M-V, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): results of MajesTEC-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6
3. FDA grants third approval under the national priority voucher program. FDA. March 5, 2026. Accessed August 21, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program