Costa Explains What Drives Survival Benefit With Tec/Dara in Myeloma

Luciano J. Costa, MD, PhD, professor of medicine and director of the Multiple Myeloma Research and Treatment Program at the O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, discusses the unique takeaways from a post hoc competing risk analysis of the randomized phase 3 MajesTEC-3 trial (NCT05083169) he presented at the International Myeloma Society Annual Meeting and Exposition.

The findings demonstrate that the combination of teclistamab (Tecvayli), a BCMA × CD3 bispecific T-cell engager, and daratumumab (Darzalex), an anti-CD38 monoclonal antibody, yields unprecedented overall survival (OS) and progression-free survival (PFS) in early relapsed/refractory multiple myeloma (RRMM). Designed for patients with 1 to 3 prior lines of therapy including a proteasome inhibitor and lenalidomide (Revlimid), the trial compared Tec-Dara () against standard daratumumab-based triplets DPd and DVd, ( which used pomalidomide (Pomalyst) or bortezomib (Velcade) respectively.

At a median follow-up of 34.5 months, Tec-Dara reduced the HR for death by 54% compared with standard triplets (; 95% CI: 0.32–0.65; ), achieving an estimated 36-month OS rate of 83.3% vs 65.0%. Beyond 10 months, Tec-Dara demonstrated a 78% reduction in mortality risk (; 95% CI: 0.13–0.38).

The OS benefit was directly driven by a dramatic decline in the cumulative incidence of progression (CIP), Costa noted in his presentation. Tec-Dara achieved a 90% reduction in the hazard of disease progression (; 95% CI: 0.07–0.16; ), with an estimated 36-month CIP of just 8.7% compared to 62.1% in the control arm.

Despite significantly longer treatment exposure, with a median duration of 32.4 months with Tec-Dara vs 16.1 months with DPd/DVd), Tec-Dara showed no decrease in safety. Nonrelapse mortality (NRM) was equivalent between arms (; ), with 36-month estimated NRM rates of 10.2% for Tec-Dara and 9.0% for DPd/DVd.

Costa emphasizes that myeloma care is shifting from a paradigm of sequential disease relapses and multiple therapeutic lines toward a model where patients receive only 1 or 2 highly effective frontline or early-relapse regimens. The immense efficacy gain of Tec-Dara, achieved without compromising safety relative to standard triplets, allows over 80% of treated patients to achieve a lifespan comparable to age-matched peers without myeloma, establishing Tec-Dara as a transformative standard of care as early as second-line RRMM. The post hoc analysis’s use of NRM and CIP emphasized that the OS benefit came with both reduced progression and lack of increased toxicity, which Costa says resonates strongly with patients.

REFERENCE

1. Costa LJ, Tannir NJ, Perrot A, et al. Overall survival, progression and non-relapse mortality with teclistamab plus daratumumab (Tec-Dara) vs Dara-based triplets in relapsed/refractory multiple myeloma (RRMM): MajesTEC3 post hoc Analysis. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.