Luciano J. Costa, Nizar J. Bahlis, Aurore Perrot, Ajay K. Nooka, Jin Lu, Charlotte Pawlyn, Roberto Mina, Gastón Caeiro, Alain Kentos, Vânia Hungria, Donna Reece, Ting Niu, Anne K. Mylin, Charlotte T. Hansen, Raphael Teipel, Britta Besemer, Meletios Α. Dimopoulos, Elena Zamagni, Satoshi Yoshihara, Kihyun Kım, Chang Ki Min, Paul A. F. Geerts, Elena van Leeuwen-Segarceanu, Agata Tyczyńska, Juan Luis Reguera, Magnus Johansson, Markus Hansson, Mehmet Turgut, Mark Grey, Surbhi Sidana, Paula Rodríguez‐Otero, Joaquín Martínez‐López, Hamza Hashmi, Robin Carson, Rachel Kobos, Weili Sun, Kristen Lantz, Anne Seifert, Deborah Briseno-Toomey, Lisa O’Rourke, Ingrid Maria Cecilia Rubin, Diego Vieyra, Lijuan Kang, María‐Victoria Mateos
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: ; 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.).