TY - JOUR
T1 - Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
AU - MajesTEC-3 Trial Investigators
AU - Costa, Luciano J.
AU - Bahlis, Nizar J.
AU - Perrot, Aurore
AU - Nooka, Ajay K.
AU - Lu, Jin
AU - Pawlyn, Charlotte
AU - Mina, Roberto
AU - Caeiro, Gaston
AU - Kentos, Alain
AU - Hungria, Vania
AU - Reece, Donna
AU - Niu, Ting
AU - Mylin, Anne K.
AU - Hansen, Charlotte T.
AU - Teipel, Raphael
AU - Besemer, Britta
AU - Dimopoulos, Meletios A.
AU - Zamagni, Elena
AU - Yoshihara, Satoshi
AU - Kim, Kihyun
AU - Min, Chang Ki
AU - Geerts, Paul
AU - Van Leeuwen-Segarceanu, Elena
AU - Tyczynska, Agata
AU - Reguera, Juan Luis
AU - Johansson, Magnus
AU - Hansson, Markus
AU - Turgut, Mehmet
AU - Grey, Mark
AU - Sidana, Surbhi
AU - Rodriguez-Otero, Paula
AU - Martinez-Lopez, Joaquin
AU - Hashmi, Hamza
AU - Carson, Robin
AU - Kobos, Rachel
AU - Sun, Weili
AU - Lantz, Kristen
AU - Seifert, Anne
AU - Briseno-Toomey, Deborah
AU - O'Rourke, Lisa
AU - Rubin, Maria
AU - Vieyra, Diego
AU - Kang, Lijuan
AU - Mateos, Maria Victoria
N1 - Publisher Copyright:
Copyright © 2025 Massachusetts Medical Society.
PY - 2026/2/19
Y1 - 2026/2/19
N2 - BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee. RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively. CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).
AB - BACKGROUND: In a phase 1-2 trial, teclistamab, a bispecific antibody targeting CD3 on T-cell surfaces and B-cell maturation antigen on myeloma cells, showed durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma. Daratumumab, a monoclonal antibody targeting CD38 protein, has shown survival benefit in patients with multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned patients with one to three previous lines of therapy to receive combination therapy with teclistamab-daratumumab or daratumumab combined with dexamethasone plus the investigator's choice of pomalidomide (DPd) or bortezomib (DVd) - the DPd or DVd group. The primary end point was progression-free survival, as assessed by an independent review committee. RESULTS: A total of 587 patients underwent randomization (291 to receive teclistamab-daratumumab and 296 to receive DPd or DVd). At a median of 34.5 months, progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. The estimated 36-month progression-free survival was 83.4% in the teclistamab-daratumumab group and 29.7% in the DPd or DVd group (hazard ratio, 0.17; 95% confidence interval, 0.12 to 0.23; P<0.001). More patients in the teclistamab-daratumumab group than in the DPd or DVd group had a complete response or better (81.8% vs. 32.1%), an overall response (89.0% vs. 75.3%), and minimal residual disease negativity (10-5; 58.4% vs. 17.1%) (P<0.001 for all comparisons). Serious adverse events occurred in 70.7% of the patients in the teclistamab-daratumumab group and in 62.4% of those in the DPd or DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively. CONCLUSIONS: In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab-daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT05083169.).
UR - https://www.scopus.com/pages/publications/105030591195
U2 - 10.1056/NEJMoa2514663
DO - 10.1056/NEJMoa2514663
M3 - Article
C2 - 41363801
AN - SCOPUS:105030591195
SN - 0028-4793
VL - 394
SP - 739
EP - 752
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 8
ER -