Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies.

Teclistamab is a B‑cell maturation antigen (BCMA)-directed bispecific antibody approved for the treatment of patients with triple-class exposed relapsed/refractory multiple myeloma. In the phase 1/2 MajesTEC-1 study, a cohort of patients who had prior BCMA-targeted therapy (antibody-drug conjugate [ADC] or CAR-T cell therapy) were enrolled to explore teclistamab in patients previously exposed to anti-BCMA treatment. At median follow-up of 28.0 months (range, 0.7-31.1), 40 patients with prior BCMA-targeted therapy had received subcutaneous 1.5 mg/kg weekly teclistamab. Median prior lines of treatment were 6 (range, 3-14). Prior anti-BCMA therapy included ADC (n = 29), CAR-T (n = 15), or both (n = 4). Overall response rate was 52.5%; 47.5% of patients achieved very good partial response or better and 30.0% achieved complete response or better. Median duration of response was 14.8 months, median progression-free survival was 4.5 months, and median overall survival was 15.5 months. The most common treatment-emergent adverse events (TEAEs) were neutropenia, infections, cytokine release syndrome, and anemia; cytopenias and infections were the most common grade ≥3 TEAEs. Infections occurred in 28 (70.0%) patients (n = 13 [32.5%] maximum grade 3/4; n = 4 [10%] grade 5). Prior to starting teclistamab, baseline BCMA expression and immune characteristics were unaffected by prior anti-BCMA treatment. The MajesTEC-1 trial cohort C results demonstrate favorable efficacy and safety of teclistamab in patients with heavily pretreated RRMM and prior anti-BCMA treatment. NCT03145181; NCT04557098.