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 standard-of-care regimens. The study demonstrated clinically meaningful and statistically significant improvements in both progression-free survival and overall survival, with TECVAYLI reducing the risk of disease progression or death by 71% and the risk of death by 40% versus standard-of-care therapies. 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 standard of care in earlier-line RRMM.

The results presented at ASCO 2026 were as follows:

Efficacy

• TECVAYLI significantly improved PFS (HR=0.29; p<0.0001) and OS (HR=0.60; p=0.0020) in a heavily pretreated population, including approximately 85% anti-CD38-refractory and 80% lenalidomide-refractory patients.

• 18 months, PFS: 69.8% with TECVAYLI vs. 26.9% in the control group.

• Deep responses were observed, with a ≥CR rate of 65.9% with TECVAYLI vs. 16.8% with the control group.

• ORR: 84.5% for patients on TECVAYLI, while only 54.2% of patients in the control group.

Safety

• Overall TEAE rates were comparable to standard of care (99.7% vs. 97.9%).

• Higher rates of Grade 3/4 TEAEs (84.9% vs. 76.3%), Grade 5 TEAEs (6.5% vs. 3.5%), and 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%).

• Median treatment duration was nearly doubled with Tec versus PVd/Kd (13.1 vs. 7.0 months), while TEAE-related discontinuations were lower (10.7% vs. 13.1%).

KOL insights

“Daratumumab plus teclistamab represents a highly potent treatment option for patients at first relapse. For patients who are not intended to receive CAR T-cell therapy, this regimen may be a preferred choice due to its potential to provide durable and long-lasting remissions while supporting a strategic long-term treatment approach.” – Expert Opinion

“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 the American Cancer Society, approximately 36,000 new cases of multiple myeloma are expected to be diagnosed in the United States, with a higher incidence observed in men than in women. Teclistamab monotherapy, a BCMA×CD3 bispecific antibody, demonstrated significant improvements in progression-free survival, overall survival, 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 US and Europe seeking approval in earlier treatment lines further underscore its potential to reshape the multiple myeloma treatment paradigm.