Results from the phase 3 MajesTEC-9 trial, presented on Day 1 of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that teclistamab monotherapy significantly improved progression-free survival (PFS) and overall survival (OS) compared with investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM) who had received 1 to 3 prior lines of therapy, including lenalidomide and an anti-CD38 monoclonal antibody. The findings were published simultaneously in the New England Journal of Medicine.
The open-label, multicenter trial enrolled patients with documented progression or lack of response to their last regimen. Patients who had received prior BCMA-directed therapy were excluded from the study. Patients were randomly assigned 1:1 to teclistamab monotherapy (n = 296) or PVd or Kd (n = 297). The primary endpoint of the study was independent review committee (IRC)–assessed PFS.
At a median follow-up of 17.3 months, median PFS was not reached with teclistamab vs 8.2 months with PVd or Kd. Estimated 18-month PFS was 69.8% vs 26.9%, respectively, corresponding to an HR for progression or death of 0.29 (95% CI, 0.23-0.38; P < .001).
The overall response was 84.5% with teclistamab vs 54.2% on PVd or Kd. Patients on the teclistamab arm had deeper responses with a complete response or better response occurring in 65.9% of patients on teclistamab vs 16.8% with PVd or Kd (P < .001). MRD-negative complete response or better was reported in 38.5% vs 6.7%, respectively.
Overall survival was also significantly improved with teclistamab treatment. The estimated 18-month OS was 79.2% with teclistamab and 68.6% with PVd or Kd, with an HR for death of 0.60 (95% CI, 0.43-0.83; P = .002).
Grade 3 or 4 adverse events occurred in 84.9% of patients receiving teclistamab and 76.3% receiving PVd or Kd. Cytokine release syndrome occurred in 66.0% of teclistamab-treated patients, mostly grade 1 or 2, and ICANS occurred in 4.1%. Grade 3 or 4 infections occurred in 41.6% and 29.0%, respectively. Grade 5 adverse events occurred in 6.5% and 3.5%, respectively. In both arms, most of the adverse event-related deaths were due to infection.
In a New England Journal accompanying editorial, María-Victoria Mateos, PhD, described MajesTEC-9 as a landmark trial that supports teclistamab monotherapy as a pragmatic and accessible BCMA-targeted approach in early relapse, while emphasizing that broader use will depend on infection prevention, patient selection, and sequencing.
Table. Key Efficacy Outcomes in MajesTEC-9
| Teclistamab (n = 296) | PVd or Kd (n = 297) | HR (95% CI); P | |
| Median PFS, mo | NR | 8.2 | 0.29 (0.23-0.38); P < .001 |
| 18-mo PFS, % | 69.8 | 26.9 | |
| Median OS, mo | NR | NR | 0.60 (0.43-0.83); P = .002 |
| 18-mo OS, % | 79.2 | 68.6 | |
| ORR, % | 84.5 | 54.2 | |
| ≥CR, % | 65.9 | 16.8 | |
| ≥MRD-negative CR, % | 38.5 | 6.7 |
Abbreviations: BCMA, B-cell maturation antigen; CR, complete response; ICANS, immune effector cell–associated neurotoxicity syndrome; Kd, carfilzomib and dexamethasone; MRD, minimal residual disease; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PVd, pomalidomide, bortezomib, and dexamethasone.
References
Mina R, et al. MajesTEC-9: Phase 3 study of teclistamab monotherapy vs investigator’s choice of PVd or Kd in patients with relapsed or refractory multiple myeloma after 1 to 3 prior lines of therapy. Presented at: ASCO Annual Meeting 2026; Day 1; Abstract 7507.
Touzeau C, Mina R, Quach H, et al; MajesTEC-9 Trial Investigators. Teclistamab in multiple myeloma with one to three previous lines of therapy. N Engl J Med. Published May 29, 2026. doi:10.1056/NEJMoa2603870
Mateos M-V. Redefining early relapse in multiple myeloma — time to change the rules. N Engl J Med. Published May 29, 2026. doi:10.1056/NEJMe2605404
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