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Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection. There is a paucity of data evaluating the utility of both serum soluble B-cell maturation antigen (sBCMA) levels and metabolic tumor volume (MTV) at baseline in patients with RRMM undergoing CAR-T therapy. We identified a cohort of 183 patients with available serum to measure sBCMA and/or pre-treatment MTV, derived from positron emission tomography-computed tomography (PET-CT) scans obtained per standard of care. Expectedly, high pre-treatment levels of sBCMA correlated with other established markers of tumor burden (e.g., bone marrow plasma cells/BMPCs, beta2 microglobulin) and inflammation, and were highly prognostic for CAR-T related toxicities and inferior progression free survival (PFS). High MTV values were also associated with shorter PFS and inferior overall survival (OS). The poor correlation observed between these two measures prompted evaluation of those with discordant results, identifying that those with low sBCMA and high MTV frequently had low/absent BCMA expression on plasma cells and suboptimal response. Our findings highlight the potential utility of sBCMA and MTV to facilitate more personalized treatment strategies in the management of RRMM eligible for BCMA directed CAR-T., (Copyright © 2024 American Society of Hematology.)