Circulating Plasma Cells in Newly Diagnosed Symptomatic Multiple Myeloma As a Prognostic Marker for Patients with Standard-Risk Cytogenetics

Abstract

Multiple Myeloma (MM) is a clonal B-cell disorder characterized by accumulation of malignant plasma cells (PCs) in the bone marrow (BM). Circulating PCs can be detected in the peripheral blood of a significant proportion of patients with MM and their presence is a well-known prognostic factor. Indeed, the appearance of circulating PCs in the blood could indicate relative indipendence from adhesion to the microenvironment, thus implying more aggressive disease. In this study, we examined the relationship between the number of PCs and citogenetic risk in patients with newly diagnosed MM. We analyzed peripheral blood from patients with Monoclonal Gammopathy of Undetermined Significance (MGUS; n=15), Smoldering Myeloma (SM; n=28), Solitary Plasmacytomas (SP; n=3) and active Multiple Myeloma (MM; n=105). These patients were followed by the U.O.C. Ematologia at the "Mazzoni" Hospital from January 2006 to December 2013, with a median follow-up of 25 months. We analyzed clinical, laboratory and cytogenetic data of patients with active MM. However, cytogenetic analysis was not evaluable for 15 patients. The number of circulating PCs was detected by flow cytometry using a simple two-colours approach. Cells were stained with fluorescence-labeled CD38 and CD45 antibodies and 50,000 events were acquired and analyzed for each patient. PCs were identified by gating on CD38bright+/CD45- cells. Using a receiver operating characteristics (ROC) analysis, we assessed that ³41circulating PCs is the optimal cut-off for defining poor prognosis. The 8-years probability of Overall Survival (OS) and Progression-Free Survival (PFS) in patients with <41 and ³41circulating PCs, was 32% vs 8% (p=0.017) and 29% vs 0% (p=0.0008), respectively. Patients with high-risk cytogenetics (n=24) had poor prognosis, independently of circulating PCs (PC<41 vs PC³41: OS=0% vs OS=16%, p=n.s.; PFS=0% vs 17%, p=n.s.). Patients with standard-risk cytogenetics (n=66) showed a better prognosis associated to a lower number of circulating PCs (PC<41 vs PC³41: OS=36% vs 10%, p=0.026; PFS=37% vs 0%, p=0.0001). These data were confirmed by multivariate analysis (Cox model) for the subgroup with standard-risk cytogenetics, in which the presence of ³41 circulating PCs, older age, DS stage >I and lack of maintenance therapy, adversely affected OS and PFS. All patients with SP showed no circulating PCs. In all cases of MGUS or SM, circulating PCs, when detected, were <20. In summary, our results suggest that the quantification of circulating PCs by flow cytometry could provide useful prognostic information in newly diagnosed MM patients with standard-risk cytogenetics. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.