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Tecvayli Plus Daratumumab Shows Large Survival Gains in Phase 3 Myeloma Trial

Investigators say the subcutaneous combination could move into earlier use if regulators agree, with infection risk managed through added immunoglobulin and antimicrobial prophylaxis.

Overview

  • At the ASH meeting, the phase 3 MajesTEC-3 trial in 587 patients with 1–3 prior therapies showed an 83% reduction in the risk of progression or death versus standard daratumumab-based regimens at a median 34.5 months of follow-up.
  • The combination cut the risk of death by 54%, with 36-month overall survival of 83.3% versus 65.0% for the control arm.
  • Deep responses were more frequent, including complete responses in about 82% on Tecvayli plus daratumumab, and higher minimal residual disease negativity than with comparator regimens.
  • Infections occurred more often with the combination (including 13 infection-related deaths reported), but incidence declined over time after protocol amendments added immunoglobulin replacement and antimicrobial prophylaxis; cytokine release syndrome was mainly low grade and resolved.
  • The regimen is given subcutaneously with monthly dosing after cycle 6 and early steroid discontinuation, and results were presented at ASH and published in the New England Journal of Medicine.