Teclistamab in multiple myeloma with one to three previous lines of therapy

Teclistamab is a bispecific antibody targeting BCMA and CD3. The multinational randomized MajesTEC-9 trial evaluated teclistamab as early-line monotherapy in relapsed or refractory multiple myeloma (R/R MM). Patients with one, two, or three previous lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, were randomized to teclistamab (n=293) or investigator’s choice of pomalide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) as control group (n=297). Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary endpoint was progression-free survival (PFS) as assessed by an independent review committee. At the interim analysis after a median follow-up of 17.3 months, teclistamab significantly improved PFS as compared with PVd or Kd (at 18 months 69.8% versus 26.3%; HR 0.29; p<0.001), as was the case for overall survival (at 18 months 79.2% versus 68.6%; HR 0.60; p=0.002). Also the percentage of patients with a complete reponse or better was higher with teclistamab than with PVd or Kd (65.9% versus 16.8%; p<0.001). Adverse events of grade 3 or 4 occurred in 84.9% of teclistamab recipients and in 76.3% of PVd or Kd recipients, with grade 5 adverse events in 6.5% and 3.5%, respectively. CRS, mostly grade 1 or 2, occurred in 66.0% of teclistamab recipients, ICANS in 4.1%, and grade 3 or 4 infection in 41.6%. The authors conclude that among patients with R/R MM and one to three previous lines of therapy, teclistamab significantly improved progression-free survival and overall survival as compared with PVd or Kd; infections of grade 3 or 4 were common.