N Engl J Med. 2026 May 29. doi: 10.1056/NEJMoa2603870. Online ahead of print.
ABSTRACT
BACKGROUND: The efficacy of teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, as early-line monotherapy in relapsed or refractory multiple myeloma is unclear.
METHODS: We randomly assigned patients with relapsed or refractory multiple myeloma who had previously received one, two, or three lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, to receive teclistamab or the investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary end point was progression-free survival as assessed by an independent review committee.
RESULTS: A total of 296 patients were assigned to teclistamab and 297 to PVd or Kd. At the interim analysis (median follow-up, 17.3 months), teclistamab significantly improved progression-free survival as compared with PVd or Kd (estimated 18-month progression-free survival, 69.8% vs. 26.9%; hazard ratio for disease progression or death, 0.29; 95% confidence interval [CI], 0.23 to 0.38; P<0.001). The percentage of patients with a complete response or better was higher with teclistamab than with PVd or Kd (65.9% vs. 16.8%, P<0.001). Overall survival was improved with teclistamab as compared with PVd or Kd (estimated 18-month overall survival, 79.2% vs. 68.6%; hazard ratio for death, 0.60; 95% CI, 0.43 to 0.83; P = 0.002). Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively. Cytokine release syndrome, mostly of grade 1 or 2, occurred in 66.0% of teclistamab recipients, and immune effector cell-associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% of teclistamab recipients and in 29.0% of PVd or Kd recipients.
CONCLUSIONS: Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survival as compared with PVd or Kd. Infections of grade 3 or 4 were common. (Funded by Johnson & Johnson; MajesTEC-9 ClinicalTrials.gov number, NCT05572515.).
PMID:42212933 | DOI:10.1056/NEJMoa2603870