Bispecific antibodies targeting B‐cell maturation antigen in multiple myeloma: Current clinical applications, challenges and future directions

Abstract

Anti‐B cell maturation antigen (BCMA) therapies, including antibody‐drug conjugates, chimeric antigen receptor T cells, and bispecific antibodies (bsAbs), have recently revolutionized the treatment landscape of multiple myeloma. This review outlines the biologic rationale for targeting BCMA and sheds light on the mechanism of action of bsAbs and the main reasons behind loss of response and treatment resistance. Moreover, available safety and efficacy information on approved agents (i.e., teclistamab, elranatamab, and linvoseltamab) are described, focusing on the most relevant treatment‐related toxicities, including cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, cytopenias, and infections, and established approaches for their monitoring and management. Furthermore, available data on active trials evaluating the use of bsAbs in combination with other agents and/or in earlier lines of therapy are discussed, as well as emerging data on novel anti‐BCMA bsAbs in clinical development, such as etentamig. Finally, the use of bsAbs beyond multiple myeloma has been explored by reviewing clinical trials and real‐world experiences in other monoclonal gammopathies (e.g., smoldering multiple myeloma and light‐chain amyloidosis) or other conditions, such as autoimmune diseases. Overall, the objective of this review was to provide a comprehensive overview on the role of BCMA‐targeting bsAbs while discussing future developments in this field, including their use across different settings and combinations strategies, as well as the ongoing efforts to improve safety and tolerability through the implementation of specific guidelines for toxicity management.