The Agony of Choice—Where to Place the Wave of BCMA-Targeted Therapies in the Multiple Myeloma Treatment Puzzle in 2022 and Beyond

SIMPLE SUMMARY: There is no doubt that immunotherapeutic approaches will change the current treatment landscape of multiple myeloma in the near future; in particular, a wave of BCMA-targeted therapies is currently entering clinical routine. Although the increasing availability of different therapeutic approaches is highly welcome, it also increases the daily challenges in clinical decision making if they all use the same target. Here, we provide a comprehensive summary of BCMA-targeted approaches in myeloma and aim to share some basic concepts in clinical decision making. ABSTRACT: Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody–drug conjugates, bispecific and trispecific antibodies, autologous and allogeneic CAR-T cell as well as CAR-NK cell constructs are either approved or in different stages of clinical and preclinical development for the treatment of MM. This armamentarium of treatment choices raises several challenges for clinical decision making, particularly in the absence of head-to-head comparisons. In this review, we provide a comprehensive overview of BCMA-targeting therapeutics, deliver latest updates on clinical trial data, and focus on potential patient selection criteria for different BCMA-targeting immunotherapeutic strategies.