CHMP Recommends Teclistamab Monotherapy in Early R/R Multiple Myeloma

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an indication extension for teclistamab (Tecvayli) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.¹

The opinion now advances to the European Commission (EC), which will make the final decision on marketing authorization across the European Union. Previousl, in August 2026, the EC approved teclistamab in combination with daratumumab (Darzalex) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy.²

The positive opinion for teclistamab monotherapy is supported by data from the phase 3 MajesTEC-9 trial (NCT05572515), where the bispcific antibody reduced the risk of disease progression or death by 71% vs standard-of-care regimens (HR, 0.29; 95% CI, 0.23-0.38; P < .0001).² At a median follow-up of 17.3 months, the median progression-free survival (PFS) was not reached with teclistamab (n = 296) vs 8.2 months with investigator's choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kypolis) and dexamethasone (Kd; n = 297); the estimated 18-month PFS rate was 69.8% vs 26.9%, respectively. Teclistamab also reduced the risk of death by 40% (HR, 0.60; 95% CI, 0.43-0.83; P = .0020), and a complete response or better (≥CR) was achieved in 65.9% of patients vs 16.8% treated with standard-of-care regimens (P < .0001).

“This positive CHMP opinion reflects the importance of teclistamab in multiple myeloma and further reinforces its potential as a foundational immunotherapy after first-line treatment,” Ester in ’t Groen, EMEA Therapeutic Area Head, Haematology, Johnson & Johnson, stated in the news release.¹

Teclistamab-cqyv monotherapy is currently not approved by the FDA, but in March 2026, the United States regulatory agency approved teclistamab 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.⁴

How was the MajesTEC-9 trial designed?

MajesTEC-9 was a phase 3, randomized study that enrolled 593 patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy including an anti-CD38 monoclonal antibody and lenalidomide (Revlimid), and who had an ECOG performance status of 0 to 2; patients with prior BCMA-directed therapy were excluded.²

Patients were randomly assigned 1:1 to teclistamab monotherapy or investigator's choice of PVd or Kd, 69% of whom received Kd.

The primary end point was PFS per independent review committee, and key secondary end points included complete response (CR) or better rate, overall survival (OS), and the MySIm-Q total symptom score, with additional secondary end points of overall response rate (ORR), safety, and pharmacokinetics; rate of minimal residual disease–negative at 10⁻⁵ sensitivity CR or better was an exploratory end point.

What additional efficacy and safety data were reported for teclistamab monotherapy?

Teclistamab produced a significantly higher ORR (84.5% vs 54.2%; odds ratio [OR], 4.62; 95% CI, 3.13-6.83; P < .0001), and it led to a CR or better rate nearly 4 times that of the control arm (65.9% vs 16.8%; OR, 10.42; 95% CI, 6.89-15.76; P < .0001).

The MRD-negative CR or better rate was 38.5% vs 6.7% in the intent-to-treat population (OR, 8.56; 95% CI, 5.14-14.26) and 86.4% vs 45.5% among MRD-evaluable patients. The estimated 18-month OS rate was 79.2% with teclistamab vs 68.6% with PVd/Kd, and PFS favored teclistamab across all evaluated subgroups, including patients with high-risk cytogenetics and anti-CD38- or lenalidomide-refractory disease. The median duration of response was not reached with teclistamab vs 13.4 months with PVd/Kd, and the median treatment duration was 13.1 months vs 7.0 months, respectively.

Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.7% of patients treated with teclistamab (n = 291), with grade 3/4 TEAEs reported in 84.9%, and grade 5 TEAEs occurred in 6.5%; these respective rates were 97.9%, 76.3%, and 3.5%, for PVd/Kd (n = 283).

Cytokine release syndrome occurred in 66.0% of teclistamab-treated patients but was mostly grade 1/2, with grade 3 events reported in 0.7% of patients and no grade 4 or 5 events noted. No discontinuations were associated with CRS. Immune effector cell–associated neurotoxicity syndrome was infrequent and generally low grade. Neutropenia was the most common grade 3/4 hematologic TEAE (54.3%).

Infections occurred in 82.8% of teclistamab-treated patients, including grade 3/4 infections in 41.6% and grade 5 infections in 5.5%, and hypogammaglobulinemia was reported in 69.1%. Grade 3 or higher infections were most frequent in the first 6 months and declined thereafter, consistent with disease control, reinforcing the need for infection prophylaxis, monitoring, and immunoglobulin replacement therapy. TEAEs led to discontinuation in 10.7% of teclistamab-treated patients vs 13.1% of those in the control arm.

What other multiple myeloma recommendations were given by CHMP?

On September 17, 2026, the CHMP adopted a positive opinion recommending an expanded indication for melflufen (Pepaxti) in combination with dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 2 prior lines of therapy and whose disease is refractory to lenalidomide and to the last line of therapy.⁴

References

1. CHMP recommends approval of Johnson & Johnson's Tecvayli (teclistamab) in relapsed/refractory multiple myeloma after at least one prior therapy. News release. Johnson & Johnson. September 18, 2026. Accessed September 18, 2026. https://www.globenewswire.com/news-release/2026/09/18/3364625/0/en/chmp-recommends-approval-of-johnson-johnson-s-tecvayli-teclistamab-in-relapsed-refractory-multiple-myeloma-after-at-least-one-prior-therapy.html
2. 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
3. Mina R, Touzeau C, Hungria V, et al. MajesTEC-9: a phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). J Clin Oncol. 2026;44(suppl 16):7507. doi:10.1200/JCO.2026.44.16_suppl.7507
4. CHMP recommends label expansion of melflufen to third-line lenalidomide-refractory multiple myeloma. OncLive. Published September 17, 2026. Accessed September 18, 2026. https://www.onclive.com/view/chmp-recommends-label-expansion-of-melflufen-to-third-line-lenalidomide-refractory-multiple-myeloma