Teclistamab Monotherapy Wins EU Approval for R/R Myeloma After at Least 1 Prior Therapy

The European Commission (EC) has approved an extension of the indication for teclistamab (Tecvayli) monotherapy to include adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy.¹

This follows the August 2026 EU approval of 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 Teclistamab monotherapy was initially approved by the EC in August 2022 for the treatment of patients with relapsed/refractory multiple myeloma who have received at least 3 prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.¹

The second-line monotherapy approval was supported by data from the phase 3 MajesTEC-9 trial (NCT05572515), in which teclistamab significantly improved progression-free survival (PFS) vs investigator's choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or carfilzomib (Kyprolis) and dexamethasone (Kd) in patients who had received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide (Revlimid).^1,3

At a median follow-up of 17.3 months, the estimated 18-month PFS rates were 69.8% with teclistamab (n = 296) vs 26.9% with PVd/Kd (n = 297), translating to a 71% reduction in the risk of disease progression or death (HR, 0.29; 95% CI, 0.23-0.38; P < .001).³ Median PFS was not reached with teclistamab vs 8.2 months with PVd/Kd. Teclistamab also improved overall survival (OS), with estimated 18-month OS rates of 79.2% vs 68.6%, respectively (HR, 0.60; 95% CI, 0.43-0.83; P = .002).

“Patients with relapsed or refractory multiple myeloma often experience shorter remissions and diminishing responses with each subsequent line of therapy, making effective treatment at first relapse increasingly important,” Cyrille Touzeau, MD, PhD, a professor at University Hospital of Nantes in France, stated in a news release.¹ “The approval of teclistamab monotherapy gives physicians an additional immunotherapy option in the second-line setting, supported by significant improvements in both progression-free and overall survival. With nearly two-thirds of patients achieving a complete response or better, the results seen with teclistamab are encouraging and demonstrate the depth of response achieved in the study.”

How was the MajesTEC-9 trial designed?

The randomized, phase 3 MajesTEC-9 trial enrolled patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, and who had an ECOG performance status of 0 to 2.³ Patients with prior exposure to BCMA-directed therapy were excluded.

Between April 28, 2023, and April 3, 2025, a total of 593 patients were randomly assigned 1:1 to receive teclistamab (n = 296) or investigator's choice of PVd or Kd (n = 297); 69% of patients in the control arm received Kd.

Teclistamab was given subcutaneously in 28-day cycles, with step-up doses of 0.06 mg/kg and 0.3 mg/kg on days 1 and 3 of cycle 1, followed by 1.5 mg/kg weekly through cycle 2, 3 mg/kg every 2 weeks in cycles 3 through 6, and 3 mg/kg every 4 weeks from cycle 7 onward. Patients with a confirmed very good partial response (VGPR) or better could switch to every-4-week dosing before cycle 7 at investigator discretion, and dexamethasone premedication was required only on days 1, 3, and 5 of cycle 1. A total of 33.7% of patients in the teclistamab arm switched to every-4-week dosing before cycle 7.

The primary end point was PFS assessed by an independent review committee per 2016 International Myeloma Working Group criteria. Key secondary end points included the rate of complete response (CR) or better, OS, and the Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) total symptom score; other secondary end points included overall response rate, safety, pharmacokinetics, and immunogenicity. Minimal residual disease (MRD)–negative CR or better at a threshold of 10⁻⁵ was an exploratory end point.

What other efficacy data supported the approval?

The PFS benefit with teclistamab was observed across all prespecified subgroups, including patients with anti-CD38–refractory disease (HR, 0.32; 95% CI, 0.24-0.42), lenalidomide-refractory disease (HR, 0.30; 95% CI, 0.23-0.40), high-risk cytogenetics (HR, 0.27; 95% CI, 0.18-0.41), International Staging System stage III disease (HR, 0.46; 95% CI, 0.26-0.83), and 1 prior line of therapy (HR, 0.34; 95% CI, 0.18-0.64).

The overall response rate was 84.5% with teclistamab vs 54.2% with PVd/Kd (odds ratio, 4.62; 95% CI, 3.13-6.83; P < .0001). The rate of CR or better was 65.9% vs 16.8%, respectively (P < .001), and the rate of VGPR or better was 80.1% vs 36.4%. Median duration of response was not estimable (95% CI, 25.2-not estimable) with teclistamab vs 13.4 months (95% CI, 10.4-17.3) with PVd/Kd, and the estimated 18-month duration-of-response rates were 80.6% vs 40.1%.

In the intent-to-treat population, MRD-negative CR or better at 10⁻⁵ was achieved by 38.5% of patients in the teclistamab arm vs 6.7% of those in the PVd/Kd arm. Among MRD-evaluable patients, the rates were 86.4% (n = 132) vs 45.5% (n = 44), respectively.

The OS benefit with teclistamab was observed even though more than two-thirds of patients in the PVd/Kd arm who initiated subsequent therapy received a bispecific antibody or CAR T-cell therapy. Teclistamab also delayed the time to worsening of MySIm-Q total symptom score (HR, 0.50; 95% CI, 0.36-0.71; P < .0001), with 18-month event-free rates of 73.5% vs 55.1%.³ Median treatment duration was 13.1 months with teclistamab vs 7.0 months with PVd/Kd.¹

What is the safety profile of teclistamab?

In the safety population, any-grade treatment-emergent adverse effects (TEAEs) occurred in 99.7% of patients treated with teclistamab (n = 291) vs 97.9% of those treated with PVd/Kd (n = 283), and grade 3/4 TEAEs occurred in 84.9% vs 76.3%, respectively.³ Grade 5 TEAEs occurred in 6.5% vs 3.5% of patients. TEAEs led to discontinuation of all study treatment in 10.7% vs 13.1% of patients, and deaths due to disease progression occurred in 8.6% vs 18.7%.

Cytokine release syndrome (CRS) occurred in 66.0% of patients treated with teclistamab and was grade 1 in 48.8%, grade 2 in 16.5%, and grade 3 in 0.7%, with no grade 4 or 5 events; all CRS events resolved, and none led to discontinuation. Immune effector cell–associated neurotoxicity syndrome occurred in 4.1% of patients, including grade 3 events in 0.3%. The most common grade 3/4 hematologic TEAE was neutropenia, which occurred in 54.3% of patients in the teclistamab arm vs 22.3% of those in the PVd/Kd arm.

Infections of any grade occurred in 82.8% vs 68.2% of patients, and grade 3/4 infections occurred in 41.6% vs 29.0%, respectively. Grade 5 infections occurred in 5.5% [16/291] vs 2.8% [8/283] of patients; 14 of the 16 fatal infections in the teclistamab arm occurred within the first 6 months. The proportion of patients in the teclistamab arm with a new-onset grade 3 or higher infection declined from 33.0% in the first 6 months to 13.9% in months 6 through 12 and 8.9% in months 12 through 18. Hypogammaglobulinemia was reported in 69.1% vs 50.2% of patients, and investigators recommended antimicrobial prophylaxis and immunoglobulin replacement therapy.

References

1. European Commission approves Johnson & Johnson's Tecvayli (teclistamab) monotherapy for relapsed/refractory multiple myeloma, expanding treatment options from first relapse. News release. Johnson & Johnson. October 23, 2026. Accessed October 23, 2026. https://www.globenewswire.com/news-release/2026/10/23/3387167/0/en/european-commission-approves-johnson-johnson-s-tecvayli-teclistamab-monotherapy-for-relapsed-refractory-multiple-myeloma-expanding-treatment-options-from-first-relapse.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 October 23, 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. Touzeau C, Mina R, Quach H, et al; MajesTEC-9 Study Investigators. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. 2026;395(5):440-453. doi:10.1056/NEJMoa2603870