Quantification of clonal circulating plasma cells in newly diagnosed multiple myeloma: Implications for redefining high-risk myeloma

The presence of clonal circulating plasma cells (cPCs) is a marker of high-risk disease in all stages of monoclonal gammopathies. However, the prognostic utility of quantitating cPCs using multiparametric flow cytometry in multiple myeloma (MM) patients with current treatments is unknown. There were 157 consecutive patients with newly diagnosed MM seen at the Mayo Clinic, Rochester from 2009 to 2011 that had their peripheral blood evaluated for cPCs by multiparameter flow cytometry. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log-rank test. Using a receiver operating characteristics (ROC) analysis, ≥400 cPCs were considered as the optimal cutoff for defining high-risk disease. The presence of ≥400 cPCs was associated with higher plasma cell (PC) proliferation and adverse cytogenetics. The median time-to-next-treatment and overall survival (OS) in patients with ≥400 cPCs (N=37, 24%) was 14 months and 32 months compared with 26 months and not reached for the rest (P<0.001). In a multivariable model, the presence of ≥400 cPCs and older age adversely affected OS. Flow cytometry to quantify cPCs is a valuable test for risk stratifying newly diagnosed MM patients in the era of novel agents. Future studies are needed to determine its role in developing a risk-adapted treatment approach.