Teclistamab Combo Earns Positive CHMP Opinion in R/R Multiple Myeloma

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended approval of an indication extension for teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior therapy, according to a news release from Johnson & Johnson.¹

The recommendation is supported by data from the phase 3 MajesTEC-3 trial (NCT05083169), which evaluated the off-the-shelf bispecific antibody combination against investigator’s choice of standard-of-care regimens. A final decision from the European Commission is pending.

What MajesTEC-3 data supported the CHMP recommendation?

At approximately 3 years of follow-up, teclistamab plus subcutaneous daratumumab reduced the risk of disease progression or death by 83.4% compared with standard of care (HR, 0.17; 95% CI, 0.12-0.23; P <.0001). More than 90% of patients who remained progression-free at 6 months (n = 249) were still progression-free at 3 years, indicating sustained disease control. Overall survival (OS) outcomes also favored the combination (HR, 0.46; 95% CI, 0.32-0.65; P <.0001), with benefit observed across all prespecified subgroups. The 3-year OS rate was 83.3% with teclistamab plus daratumumab vs 65.0% with standard of care. Both the progression-free survival (PFS) and OS benefits were statistically significant and clinically meaningful, according to the developer.

What was the safety profile of teclistamab plus daratumumab?

The combination demonstrated a safety profile consistent with the established profiles of the individual agents. All cases of cytokine release syndrome were grade 1 or 2, did not lead to treatment discontinuation, and eventually resolved. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) were comparable between the combination and standard of care arms (95.1% vs 96.6%), with cytopenia and infection most commonly observed. Grade 3 or higher infections decreased over time with immunoglobulin supplementation, infection prophylaxis, and a switch to monthly dosing. Discontinuations due to TEAEs were low and similar between arms (4.6% vs 5.5%).

“This CHMP opinion marks an important step towards establishing the off-the-shelf immunotherapy combination of teclistamab plus daratumumab as a new standard of care earlier in the treatment pathway for multiple myeloma,” said Ester in’t Groen, EMEA therapeutic area head of Hematology at Johnson & Johnson, in the press release.¹

What is the MajesTEC-3 trial design?

MajesTEC-3 is an ongoing randomized phase 3 study evaluating teclistamab plus subcutaneous daratumumab (n = 291) vs investigator’s choice of subcutaneous daratumumab and dexamethasone with either pomalidomide (Pomalyst) or bortezomib (Velcade; DPd/DVd; n = 296) in patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

The primary end point is PFS. Secondary end points include complete response or better, overall response rate, minimal residual disease negativity, OS, time to worsening of symptoms, and safety.

How does teclistamab work, and what is its approval history?

Teclistamab is an off-the-shelf subcutaneous bispecific antibody that redirects T cells through 2 targets, BCMA and CD3, to activate the immune system against myeloma cells. Daratumumab is a CD38-directed antibody that modulates the immune microenvironment and enhances T-cell activity.

Teclistamab received European Commission approval in August 2022 for patients with relapsed or refractory multiple myeloma who had received at least 3 prior therapies.² Previously, the FDA approved teclistamab plus daratumumab hyaluronidase-fihj (Darzalex Faspro) for relapsed or refractory disease after at least 1 prior line of therapy in March 2026.³

References

1. CHMP recommendation advances Johnson & Johnson’s Tecvayli (teclistamab) plus daratumumab as a potential standard of care for relapsed/refractory multiple myeloma. News release. Johnson & Johnson. June 26, 2026. Accessed June 26, 2026. https://tinyurl.com/3vfnudm4
2. Janssen marks first approval worldwide for TECVAYLI® (teclistamab) with EC authorisation of first-in-class bispecific antibody for the treatment of patients with multiple myeloma. News release. Jansen. August 24, 2022. Accessed June 26, 2026. https://bit.ly/3wsRYFP
3. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed June 26, 2026. https://tinyurl.com/45hhbpau