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B-cell maturation antigen (BCMA), selectively expressed on malignant plasma cells, has emerged as a pivotal immunotherapeutic target. BCMA-directed therapies, including chimeric antigen receptor T cells and bispecific antibodies, have achieved unprecedented response rates in relapsed\/refractory multiple myeloma (RRMM), yet their application into clinical practice is challenged by unique toxicities and resistance mechanisms. Summary: This review synthesizes current evidence on balancing the efficacy and toxicity of BCMA-targeted therapies. It details the mechanisms driving key immune-related toxicities including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome and delayed neurotoxicities. It also explores major resistance pathways such as BCMA antigen loss via genomic deletion or \u03b3-secretase-mediated shedding. The article further evaluates risk-stratified management framework and discusses strategies to overcome resistance. Key Messages: Optimizing the sequencing of BCMA-directed therapies, along with developing novel combination and multi-targeting strategies, is critical to improving long-term outcomes in RRMM.<\/jats:p>","DOI":"10.1159\/aha\/abkag002","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:47:38Z","timestamp":1790164058000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Navigating the Immune Landscape: Balancing Efficacy and Toxicity of B-Cell Maturation Antigen-Targeting Agents in Multiple 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