A Type II variation application has been submitted to the European Medicines Agency (EMA) seeking the approval of a label extension for teclistamab (Tecvayli) in combination with subcutaneous daratumumab (Darzalex; daratumumab SC) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior therapy.1
The application is based on findings from the phase 3 MajesTEC-3 trial (NCT05083169) in which treatment with teclistamab and daratumumab SC led to an 83.4% reduction in the risk of disease progression or death vs daratumumab SC plus dexamethasone and either pomalidomide (Pomalyst; DPd) or bortezomib (Velcade; DVd; HR, 0.17; 95% CI, 0.12-0.23; P < .0001).2
Additionally, over 90% of patients who remained progression-free at 6 months (n = 249) remained progression-free at 3 years. Based on the demonstrated statistically significance of the data, the Independent Data Monitoring Committee recommended unblinding the study.1
In addition to the EMA submission, Johnson & Johnson has submitted a supplemental biologics license application to the FDA seeking the approval of teclistamab and daratumumab SC in the same indication.
“There remains a critical need for off-the-shelf treatment options that can achieve deep and durable responses at second line, when immune function is better preserved,” Ester in ’t Groen, EMEA Therapeutic Area Head, Haematology, Johnson & Johnson Innovative Medicine, stated in a news release. “Teclistamab and daratumumab SC is the first off-the-shelf immunotherapy combination to demonstrate significant improvements in progression-free and overall survival [OS] in relapsed/
refractory multiple myeloma as early as second line treatment, compared to current standards of care.”
The Global State of Teclistamab Plus Daratumumab SC in Relapsed/Refractory Myeloma
- EMA and FDA submissions seek to expand teclistamab’s label for use with SC daratumumab in relapsed/refractory multiple myeloma after at least 1 prior line of therapy.
- In MajesTEC-3, the combination reduced the risk of disease progression or death by 83% vs DPd/DVd and delivered strong 3-year PFS and OS benefits.
- Grade 3/4 adverse effects were comparable with standard regimens, with cytopenias and infections being the most common toxicities.
How was the MajesTEC-3 trial conducted and what were the objectives?
MajesTEC-3 is an ongoing, phase 3 randomized study comparing the safety and activity of teclistamab plus daratumumab SC (n = 291) with investigator’s choice of DPd or DVd (n = 296) in patients with relapsed/refractory multiple myeloma who have received between 1 and 3 prior lines of therapy.2 The primary end point of the study is progression-free survival (PFS) and secondary end points include complete response or better, overall response rate, minimal residual disease negativity at a sensitivity of 10⁻⁵ by next-generation sequencing, OS, time to worsening of symptoms, and safety.
Additional data presented at the 2025 ASH Annual Meeting & Exposition indicated that with median follow-up of 34.5 months, the median PFS was not reached in the investigational arm vs 18.1 months in the DPd/DVd arm. The 36-month PFS rates were 83.4% and 29.7%, respectively.
Moreover, the addition of teclistamab to daratumumab SC produced a 3-year OS rate of 83.3% vs 65.0% with the comparator regimens, reflecting a 54% reduction in the risk of death with the investigational treatment (HR, 0.46; 95% CI, 0.32-0.65; P < .0001).
What was the safety profile of the regimen?
Comparable rates of grade 3/4 treatment-emergent adverse effects were seen with teclistamab plus daratumumab SC and the standard regimens used as the comparator, at 95.1% and 96.6%, respectively. The most frequent grade 3/4 adverse effects were cytopenia and infection. Any-grade and grade 3/4 infections occurred in 96.5% and 54.1% of patients in the investigational arm, respectively, and 84.1% and 43.4% of those in the comparator arm.
“Johnson & Johnson is committed to redefining what’s possible in multiple myeloma. An integral part of this strategy involves using the right medicines as early as possible and combining and sequencing them to achieve the best outcomes,” Jordan Schecter, MD, vice president, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine, added in a news release. “Today’s submission to the EMA reinforces this approach. Daratumumab has become a cornerstone of care for patients with newly diagnosed multiple myeloma, and by combining it with teclistamab, we see the potential to advance outcomes for relapsed patients as early as second line.”
References
- Johnson & Johnson submits application to the European Medicines Agency for Tecvayli (teclistamab) in combination with Darzalex (daratumumab) subcutaneous formulation for patients with relapsed/refractory multiple myeloma. News release. Johnson & Johnson. January 6, 2026. Accessed January 6, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-submits-application-to-the-european-medicines-agency-for-tecvayli-teclistamab-in-combination-with-darzalex-daratumumab-subcutaneous-formulation-for-patients-with-relapsed-refractory-multiple-myeloma
- Mateos MV, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): results of majestec-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6
