The U.S. Food and Drug Administration has granted traditional approval to teclistamab (Tecvayli) in combination with daratumumab and hyaluronidase-fihj (Darzalex Faspro) for adults with relapsed or refractory Multiple Myeloma who have received at least one prior treatment. The agency also converted teclistamab as a single therapy from accelerated approval to full approval.
The decision is based on results from the Phase 3 MajesTEC-3 trial, which compared the new combination with standard treatment options. After a median follow-up of 34.5 months, the teclistamab group showed much better outcomes. The median progression-free survival had not yet been reached, compared with 18.1 months in the control group. The overall response rate was 89% versus 75.3%, and 81.8% of patients achieved a complete response or better, compared with 32.1% in the control arm. In addition, 58.4% of patients reached minimal residual disease–negative status, and the 36-month overall survival rate was 83.3%, compared with 65% in the control group.
The safety profile was consistent with the known effects of the drugs. Common side effects included neutropenia, cytokine release syndrome, and diarrhea. Most cytokine release syndrome events were mild and resolved without severe complications. The treatment uses a step-up dosing approach for teclistamab, later moving to once-monthly dosing, while daratumumab also transitions to monthly administration. The trial enrolled patients who had received one to three prior therapies, including a proteasome inhibitor and lenalidomide, but excluded those previously treated with BCMA-targeted therapies or resistant to anti-CD38 antibodies.