Multinational phase 3 trial of teclistamab plus daratumumab in relapsed or refractory multiple myeloma

Teclistamab is a bispecific antibody targeting CD3 on T-cell surfaces and BCMA on myeloma cells, and daratumumab is a monoclonal antibody targeting CD38. The multinational phase 3 MajesTEC-3 trial evaluated the combination of teclistamab and daratumumab in patients with one to three previous lines of therapy for relapsed or refractory multiple myeloma (RRMM). The trial included 587 patients who were randomized 1:1 to teclistamab-daratumumab (n=291) or daratumumab and dexamethasone plus investigator’s choice of pomalide or bortezomib (DPd/DVd; n=296). The primary endpoint was progression-free survival by independent review. The median duration of follow-up was 34.5 months. The progression-free survival was significantly longer with teclistamab-daratumumab than with DPd or DVd. More patients in the teclistamab-daratumumab group than in de DPd/DVd group had a complete response or better (81.8% versus 32.1%), an overall response (89.9% versus 75.3%), and minimal residual disease negativity at 10^-5 (58.4% versus 17.1%) (p<0.001 for all comparisons). Serious adverse events occurred in 70.7% of patients in the teclistamab-daratumumab group and 62.4% of patients in the DPd/DVd group; death from adverse events occurred in 7.1% and 5.9%, respectively. The authors conclude that in patients with RRMM who received one to three previous lines of therapy, teclistamab-daratumumab resulted in longer progression-free survival than DPd/DVd.