Teclistamab (TECVAYLI), the first-in-class BCMA×CD3 bispecific T-cell engager approved for multiple myeloma, has emerged as a transformative treatment option for patients with RRMM. Developed entirely by Johnson & Johnson, TECVAYLI has demonstrated deep and durable responses in heavily pretreated patients and has helped establish bispecific antibodies as a key therapeutic class in multiple myeloma. Building on its initial FDA approval as a monotherapy for later-line RRMM in 2022, the therapy has continued to expand its clinical utility into earlier lines of treatment. In March 2026, the US FDA approved the combination of TECVAYLI and DARZALEX FASPRO for adults with RRMM who had received at least one prior line of therapy, marking a significant advancement in earlier-line treatment.

A Phase III MajesTEC-9 trial was designed to evaluate TECVAYLI much earlier in the treatment journey, including patients at first relapse or as second line, and to directly compare it with established SoC regimens. The study demonstrated clinically meaningful and statistically significant improvements in both progression-free survival and overall survival. In a population predominantly refractory to lenalidomide and anti-CD38 therapies, these findings underscore the potential of TECVAYLI to address a significant unmet need and support its emergence as a potential new SoC in earlier-line RRMM.

The results presented at EHA 2026 were as follows:

Key Efficacy Highlights:

• Teclistamab significantly improved PFS versus PVd/Kd, reducing the risk of progression or death by 71% (HR 0.29; p<0.0001)

• Median PFS was not reached with Teclistamab vs 8.2 months with PVd/Kd 

• 18-month PFS rates were 69.8% vs 26.9% 

• Overall Survival was significantly improved, with a 40% reduction in the risk of death (HR 0.60; p=0.0020)

• Complete response or better (≥CR) rates: 65.9% vs 16.8%; (OR 10.42; p<0.0001).

Key Safety Highlights:

• TEAE rates were comparable to the SoC: 99.7% with Teclistamab vs 97.9% with PVd/Kd 

• Higher rates of Grade 3/4 TEAEs: 84.9% vs 76.3% 

• Grade 5 TEAEs: 6.5% vs 3.5%

• Grade 3/4 infections: 41.6% vs 29.0% were reported with TECVAYLI.

• CRS was common (66.0%) but predominantly low grade, while ICANS was infrequent (4.1%)

• Treatment duration was nearly doubled with TECVAYLI (13.1 vs 7.0 months), with lower discontinuation due to TEAEs.

KOL insights

“In the MajestTEC-9 trial, the significant PFS and OS advantage seen with teclistamab monotherapy supports moving this bispecific antibody earlier in the treatment paradigm and reinforces its potential role as a new SOC option for patients with relapsed/refractory multiple myeloma after 1 to 3 prior lines of therapy.”– Expert Opinion

Conclusion

According to DelveInsight in 2025, there were 30,347 symptomatic incident cases of multiple myeloma in the United States. The multiple myeloma treatment landscape continues to evolve rapidly, with increasing adoption of combination regimens reshaping frontline care. The treatment landscape for multiple myeloma has expanded significantly with multiple drug classes targeting distinct disease pathways. Teclistamab monotherapy, a BCMA×CD3 bispecific antibody, demonstrated significant improvements in PFS, OS, and depth of response in heavily pretreated RRMM patients, while maintaining a manageable safety profile. These findings support the growing role of bispecific antibodies as early-relapse treatment options and highlight teclistamab’s potential as a convenient, steroid-sparing therapy across diverse clinical settings. Regulatory submissions in the United States and Europe seeking approval in earlier treatment lines further underscore its potential to reshape the multiple myeloma treatment paradigm.