CHMP Backs TECVAYLI (teclistamab) Monotherapy in Second-Line Relapsed/Refractory Multiple Myeloma
核心洞察
The EMA's CHMP has recommended extending TECVAYLI (teclistamab) approval to adults with relapsed/refractory multiple myeloma (搜索) after at least one prior therapy.
The recommendation rests on the Phase 3 MajesTEC-9 study, in which teclistamab monotherapy cut the risk of disease progression or death by 71% versus standard of care.
Teclistamab also reduced the risk of death by 40% and produced a complete response or better in 65.9% of patients versus 16.8% with PVd or Kd.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (搜索) has recommended approval of an indication extension for TECVAYLI (teclistamab) as a monotherapy in adult patients with relapsed or refractory multiple myeloma (搜索) (RRMM) who have received at least one prior therapy, Johnson & Johnson announced.
The positive opinion moves teclistamab, a BCMA (搜索)-directed bispecific T-cell engager, into a substantially earlier line of treatment than its current European label, which covers patients who have received at least three prior therapies including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and who progressed on the last therapy.
MajesTEC-9 Efficacy Data
The recommendation is supported by results from the randomized Phase 3 MajesTEC-9 study (NCT05572515), which compared teclistamab monotherapy with pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). The trial enrolled patients with RRMM who had received one to three prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.
Teclistamab demonstrated a 71% reduction in the risk of disease progression or death compared with standard of care (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.23-0.38; p<0.001). The risk of death fell by 40% (HR, 0.60; 95% CI, 0.43-0.83; p=0.002). Both progression-free survival, the study's primary endpoint, and overall survival improved significantly.
All key secondary endpoints also favored teclistamab. Nearly two-thirds of patients treated with teclistamab achieved a complete response or better (65.9% versus 16.8% with PVd or Kd; p<0.001). Secondary endpoints in MajesTEC-9 include complete response or better, duration of response, overall survival, safety and patient-reported outcomes.
Safety Profile
The safety profile observed in MajesTEC-9 was consistent with that established in prior studies of teclistamab. The median duration of treatment was almost twice as long with teclistamab as with standard of care (13.1 months versus 7.0 months), with similar overall rates of adverse events (99.7% versus 97.9%).
Grade 3/4 adverse events occurred in 84.9% of teclistamab recipients compared with 76.3% of those receiving PVd or Kd, and Grade 5 adverse events occurred in 6.5% versus 3.5%, respectively. Infections were more frequent with teclistamab than with standard of care (Grade 3/4, 41.6% versus 29.0%), although rates of Grade 3 or higher infections decreased over time.
Earlier Second-Line Approval in Combination
The CHMP opinion follows the recent European Commission approval of teclistamab in combination with daratumumab for adult patients with relapsed or refractory multiple myeloma (搜索) who have received at least one prior therapy. That decision was based on the MajesTEC-3 study, published in The New England Journal of Medicine. Together, the two Phase 3 studies support the potential of teclistamab-based regimens across a broad second-line population.
Teclistamab received European Commission approval in August 2022 for RRMM patients with at least three prior therapies. In August 2023, the EC approved a Type II variation allowing a reduced dosing frequency of 1.5 mg/kg every two weeks for patients who had achieved a complete response or better for a minimum of six months. In August 2026, the EC approved a further Type II variation for teclistamab in combination with daratumumab as early as second line.
Mechanism and Administration
Teclistamab is an off-the-shelf bispecific antibody administered as a subcutaneous injection. It redirects T-cells through two cellular targets, BCMA (搜索) and CD3 (搜索), to activate the immune system against myeloma cells. The agent is being evaluated in several combination studies, and more than 30,700 patients have been treated worldwide to date. In line with EMA regulations for new medicines and those granted conditional approval, teclistamab remains subject to additional monitoring.
Disease Burden
Multiple myeloma (搜索) is a blood cancer affecting plasma cells in the bone marrow, where malignant plasma cells proliferate, accumulate and crowd out normal blood cells, often causing bone destruction and other serious complications. In the European Union, more than 35,000 people were estimated to be diagnosed with multiple myeloma in 2024, and more than 21,900 patients died. Patients experience relapses that become more frequent with each line of therapy, while remissions become progressively shorter. Symptoms can include bone fracture or pain, low red blood cell counts, fatigue, high calcium levels, infections or kidney damage.