Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy

Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy Published May 29, 2026 N Engl J Med 2026;395:440-453 DOI: 10.1056/NEJMoa2603870 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.) Are you a member of an institution such as a university or hospital?Learn more about Institutional Access Notes This article was published on May 29, 2026, at NEJM.org. A data sharing statement provided by the authors is available with the full text of this article at NEJM.org. Supported by Johnson & Johnson. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. We thank the patients who participated in the trial and their families and caregivers; the physicians, nurses, and staff members at each site; the members of the trial safety committee; Sandre Pritchard, B.A., and Ravi Arvapally, Ph.D., for assistance with data management; Amit Apte, M.S., for assistance with programming; additional members who were involved in the data collection and analysis; and Laura Ganser, Ph.D., and Holly Clarke, Ph.D., C.M.P.P., of Lumanity Communications, for medical writing and editorial assistance with an earlier version of the manuscript. Supplementary Material Information & Authors Information Published In Copyright Copyright © 2026 Massachusetts Medical Society. All rights reserved. For personal use only. Any commercial reuse of NEJM Group content requires permission. History Published online: May 29, 2026 Published in issue: July 30, 2026 Topics Authors Metrics & Citations Metrics Altmetrics Citations Export citation Select the format you want to export the citation of this publication. 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