Teclistamab (Tecvayli) combined with daratumumab has emerged as a strong second-line treatment option for patients with relapsed or refractory multiple myeloma, especially for those who relapse after frontline quadruplet therapy and are not candidates for CAR T-cell therapy.
In the phase 3 MajesTEC-3 trial involving 587 patients, the combination significantly outperformed standard therapy. Median progression-free survival was not reached in the combination group compared with 18.1 months in the control group, with a 36-month PFS rate of 83.4% versus 29.7%. Complete response rates were 81.8% versus 32.1%, and MRD negativity rates were 58.4% versus 17.1%. Overall survival also improved, with a 36-month rate of 83.3% versus 65.0%.
Although infection rates were higher with the combination, deaths were fewer overall. Cytokine release syndrome occurred in 60.1% of patients but was mostly low grade. In real-world practice, preventive strategies such as tocilizumab, steroids, and IVIG have significantly reduced complications and improved outpatient safety.