Clinical Significance and Molecular Characteristics of Circulating Plasma Cells in Multiple Myeloma

Abstract Multiple myeloma (MM) is one of the most common hematological malignancies and remains incurable to date. Clonal plasma cells can be detected in the peripheral blood of most MM patients, and previous studies have shown an association between the quantification of circulating plasma cells (CPC) and prognosis. However, the significance of CPC for response assessment and prognosis prediction as well as the mechanism underlying CPC formation in Chinese population has not been fully elucidated. In this investigation, we used multi-parameter flow cytometry (MFC) for CPC quantification and next-generation sequencing (NGS) technology for mutational landscape mapping to identify the correlation of CPC level with clinical characteristics and the mutations. As a result, we demonstrated that CPC quantification could effectively mirror the tumor load, and CPC≥0.105% at diagnosis or detectable CPC after therapy indicates poor treatment response and adverse outcome, and it is verified that the introduction of CPC level into the R-ISS system enables a more accurate risk stratification. We also noticed an elevated percentage of light-chain MM in patients with high CPC, this is the first time, to the best of our knowledge, to report the subtype pattern regarding CPC. Mutational landscape revealed that TP53 mutations and pathways involving chromatin or chromosome regulation and adhesion may be potential mechanisms accounting for CPC formation. Accordingly, the detection of CPC by MFC may provide a less-invasive, convenient and, more importantly, reliable approach for risk stratification and disease monitoring in Chinese population.