Relapsed/Refractory Multiple Myeloma: MajesTEC-9 and Teclistamab Monotherapy in Lenalidomide and Anti-CD38 Double-Refractory Disease

Dr. Thomas Martin introduces the fourth abstract review, and Team Myeloma Masters presents MajesTEC-9, the phase 3 study of teclistamab monotherapy versus investigator's choice of standard, non-CD38-containing regimens in patients who are both lenalidomide- and anti-CD38-refractory after prior lines of therapy. The presentation frames this as a more US-representative, daratumumab-exposed population and highlights the progression-free and overall survival advantages, higher response and MRD-negativity rates, and a safety profile marked by high-grade infections offset by low rates of neurotoxicity, transient cytokine release syndrome, and an absence of enterocolitis or Parkinsonism. The cross-team debate, moderated by Dr. Martin, weighs the clinical relevance of the trial given the increasing use of daratumumab-lenalidomide maintenance, whether the control arm was suboptimal and how that shapes interpretation of the hazard ratio, the optimal duration of bispecific therapy and the case for fixed-duration dosing, and the sequencing implications of BCMA-directed therapies, including antigen escape and T-cell exhaustion when a bispecific precedes CAR T-cell therapy or vice versa. The segment closes on how to choose between teclistamab plus daratumumab and teclistamab monotherapy based on a patient's anti-CD38 exposure and refractory status.