MajesTEC-3: Tec + Dara vs Dara-based SoC regimens for RRMM

Results from the phase III MajesTEC-3 trial evaluating teclistamab + daratumumab (Tec + Dara) vs Dara-based standard-of-care (SoC) regimens in patients with relapsed/refractory multiple myeloma (RRMM) were presented by María-Victoria Mateos at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9, 2025, Orlando, US. The study included 587 patients with RRMM who had received 1–3 prior lines of therapy (LOT). The primary endpoint was progression-free survival (PFS) per independent review committee (IRC).

Key data: The median PFS was not reached in the Tec + Dara cohort vs 18.1 months in the SoC cohort. The 36-month PFS was superior in patients receiving Tec + Dara vs SOC (83.4% vs 29.7%, with a plateauing curve after ~6 months; hazard ratio [HR], 0.17). Tec + Dara had a higher overall response rate (ORR; 89.0% vs 75.3%), complete response or better (≥CR) rate (81.8% vs 32.1%), minimal residual disease (MRD)-negative (x10^-6) ≥CR rate (7.5% vs 41.8% in evaluable patients), and 36-month overall survival (OS) rate (83.3% vs 65.0%). Rates of Grade ≥3 infections were higher in the first 6 months with Tec + Dara vs SoC (35.3% vs 20.7%) but were comparable after 6 months and decreased with time.

Key learning: Tec + Dara demonstrated superior efficacy over Dara-based SoC regimens in patients with RRMM who have received 1–3 prior LOT, with superior PFS, ORR, ≥CR rate, MRD-negative ≥CR rate, and OS. The findings support the potential for community adoption of Tec + Dara.