Teclistamab for Relapsed or Refractory Multiple Myeloma: A Review of Efficacy, Safety, Resistance Mechanisms and Future Directions

Abstract

Teclistamab is the first bispecific antibody targeting B-cell maturation antigen (BCMA) approved for the treatment of relapsed or refractory multiple myeloma. Its significant efficacy as monotherapy, particularly in the Phase 1/2 MajesTEC-1 trial, has been also confirmed in the context of combination therapies. Early safety events are dominated by grade 1 or 2 cytokine release syndrome. Risk of infection is now better characterized and can be managed through systematic prophylaxis. Notably, real-world studies have confirmed its efficacy and safety, notably in patients under-represented or ineligible for clinical trials (elderly, with renal impairment or central nervous system involvement). Mechanisms of resistance to teclistamab including target loss and T-cell environment are increasingly understood. Consequently, several strategies to overcome immune escape or antigen loss are currently being evaluated in clinical trials. The use of teclistamab in earlier lines of treatment and in combination may yield better results and is evaluating but ongoing Phase 3 clinical trials.