J&J's teclistamab plus daratumumab gets CHMP backing for myeloma

Johnson & Johnson has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP), recommending approval of an indication extension for teclistamab (TECVAYLI) in combination with daratumumab. If adopted by the European Commission, the label change would allow the bispecific antibody to be used in adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy, moving it considerably earlier in the treatment pathway than its current positioning.

The recommendation is supported by data from the Phase 3 MajesTEC-3 study (NCT05083169), which compared teclistamab plus daratumumab subcutaneous formulation against investigator's choice of daratumumab-based doublet regimens in patients who had received between one and three prior lines of therapy. The trial enrolled 587 patients across the two arms.

What the data show

The headline efficacy figures are striking. At close to three years of follow-up, patients receiving the combination had an 83% reduction in the risk of disease progression or death compared to standard of care, with a hazard ratio of 0.17 (95% CI, 0.12–0.23; p less than 0.0001). Overall survival also favoured the combination, with a hazard ratio of 0.46 (95% CI, 0.32–0.65; p less than 0.0001). Three-year overall survival rates were 83.3% for the combination arm and 65.0% for the control arm.

Durability of response was a notable feature of the dataset. Of the 249 patients who remained progression-free at the six-month mark, more than 90% were still progression-free at three years, suggesting a substantial plateau effect.

On safety, all cases of cytokine release syndrome were Grade 1 or 2 and resolved without treatment discontinuation. Rates of Grade 3/4 treatment-emergent adverse events were broadly comparable between the combination and the control arm (95.1% versus 96.6%), with cytopenia and infection the most frequent events. Discontinuation rates due to adverse events were low in both arms.

"More than 90% of patients receiving the combination who were progression-free at six months remained progression-free at three years, highlighting the potential for durable long-term disease control," said Ester in 't Groen, EMEA Therapeutic Area Head for Haematology at Johnson & Johnson.

Market and competitive context

The CHMP opinion lands in a multiple myeloma landscape that is arguably the most competitive in haematological oncology. The move to offer a bispecific antibody combination at second line, rather than reserving it for later-line disease, reflects a broader strategic pattern across the sector: developers of T-cell redirecting therapies are pushing indication creep towards earlier treatment settings, where immune function is less compromised and response durability tends to be greater.

Teclistamab targets both BCMA on myeloma cells and CD3 on T-cells. Daratumumab, a CD38-directed monoclonal antibody, has been a backbone agent in myeloma for over a decade and is already used widely in frontline and relapsed settings. Their combination is mechanistically complementary rather than redundant.

Teclistamab faces direct competition from other BCMA-directed bispecifics, including elranatamab (Pfizer) and linvoseltamab (Regeneron), as well as from BCMA-targeted CAR-T therapies such as idecabtagene vicleucel and ciltacabtagene autoleucel. The ready-to-use, off-the-shelf nature of the bispecific approach remains a logistical advantage over CAR-T in a second-line setting, where manufacturing timelines and infrastructure requirements are significant practical constraints.

Teclistamab was first granted EC approval in August 2022 for heavily pre-treated patients with at least three prior lines of therapy. A positive EC decision on the new indication, which typically follows a CHMP opinion within two months, would represent a material commercial expansion of the asset's addressable population. More than 26,000 patients have been treated with teclistamab worldwide to date.