Revolutionizing 2L+ Myeloma: A Podcast on the New Era of BCMA-Targeted Bispecific Antibody Therapies

Daratumumab-based triplet and quadruplet regimens have significantly improved patient outcomes as first-line (1L) treatment in newly diagnosed multiple myeloma (MM). However, with the evolution of available 1L combination regimens, the proportion of patients with exposure and refractoriness to multiple treatment classes at first relapse is increasing. Patients experience worsening prognosis with each successive relapse, and attrition rates increase with each line of therapy (LOT). Therefore, in the second-line setting and beyond (2L+), it is critical to use the most effective treatment available up front to optimize patient outcomes. Treatments that target the B-cell maturation antigen (BCMA), particularly chimeric antigen receptor T-cell therapy, are rapidly becoming a new 2L+ standard of care (SOC). Other BCMA-targeted options, including combinations of belantamab mafodotin plus dexamethasone with bortezomib or pomalidomide, have shown promising efficacy in the 2L+ setting. BCMA-targeted bispecific antibodies are a new treatment option being explored in earlier LOTs and offer patients a steroid-sparing approach with the potential for use across all practice settings. Teclistamab combined with daratumumab is approved in the United States for patients with ≥ 1 prior LOT based on results of the phase 3 MajesTEC-3 trial, in which teclistamab-daratumumab significantly improved progression-free and overall survival versus SOC in patients with 1 to 3 prior LOTs. Several other clinical trials of BCMA-targeted bispecific antibodies in earlier LOTs are ongoing, including teclistamab monotherapy (MajesTEC-9), teclistamab combined with the G protein-coupled receptor class C group 5 member D (GPRC5D)-targeted bispecific antibody talquetamab (MonumenTAL-6), elranatamab (MagnetisMM-5), and linvoseltamab (LINKER-MM3), paving the way for the next evolution of treatment options for patients following first relapse. In this podcast, 2 leading hematologists discuss the unmet needs in 2L+ MM, considerations for treatment decisions, and the evolving treatment landscape with a focus on BCMA-targeted bispecific antibodies, a rapidly advancing class of treatments in this setting. Podcast (MP4 179036 KB).