B02 | Circulating plasma cells drive disease dissemination in multiple myeloma, independent of clonality

Multiple myeloma (MM) is a hematologic malignancy defined by clonal proliferation of plasma cells (PCs) within the bone marrow (BM), with occasional migration into peripheral blood (PB) as circulating plasma cells (CPCs). Despite substantial advances in therapy and improved patient (pt) outcomes, relapse remains common, possibly due to the capacity of BM-resident PCs to detach from the marrow niche and generate CPC clones that facilitate extramedullary spread and disease dissemination.This study assessed the relationship between CPCs and disease dissemination using imaging (DWI and PET), and evaluated biological and clinical differences between pts with monoclonal CPCs (mCPCs) and polyclonal CPCs (pCPCs).A total of 140 newly diagnosed MM pts were enrolled. BM aspirates, PB samples, imaging, and genomic data were collected at diagnosis. Multiparametric flow cytometry (sensitivity ≥10⁻⁵) was employed to enumerate and characterize CPCs; pCPCs were defined by a cytoplasmic Igκ/Igʎ ratio between 0.5 and 4.CPCs were detected in 112/140 pts (80%) with a median frequency of 0.02% (range 0.002–17.84%), while 28 pts (20%) had no detectable CPCs. Among CPCs-presenting pts, 83 (74%) harbored mCPCs (median 0.025%) and 29 (26%) had pCPCs (median 0.018%). CPCs presence correlated with higher-risk genomic profiles (IMWG-CGS; p=0.044) and unfavorable biochemical parameters—lower hemoglobin, reduced albumin, elevated beta-2 microglobulin (p