Teclistamab in Relapsed or Refractory Multiple Myeloma

Abstract

The MajesTEC-1 trial results reported by Professor Moreau and colleagues of the phase Ib/II clinical trial of teclistamab, an off-the-shelf novel B-cell maturation antigen (BCMA)-CD3 bispecific antibody drug in patients with relapsed or refractory multiple myeloma (RRMM), represent a potential paradigm shift in the treatment of RRMM.

Out of a crowded field of similar drugs in development, these results place teclistamab in the pole position for potentially being the first agent in this class to receive FDA approval in RRMM based on the high rates of durable and deep responses seen in this study. Although the depth and high rate of responses are impressive, the study highlights two challenges to the implementation of this drug in clinical practice. Management of initiation of the drug may be complex, assuming that patients may need hospital admission for initial step-up doses of teclistamab to reduce the risk of cytokine release syndrome (CRS). Importantly, a safety signal for infection was noted, with several deaths in the trial from COVID-19 and pneumonia, likely related to the significant rates of hypogammaglobulinemia caused by the continuous BCMA-directed therapy. In summary, the MajesTEC-1 study shows that teclistamab is a powerful new agent in the toolbox for clinicians managing RRMM, with the important caveats that the management of CRS and reduction of risks of infection will require careful attention and preventive strategies.