Quantification of circulating clonal plasma cells via multiparametric flow cytometry identifies patients with smoldering multiple myeloma at high risk of progression

Abstract

The presence of high numbers of circulating clonal plasma cells (cPCs) in patients with smoldering multiple myeloma (SMM), detected by a slide-based immunofluorescence assay, has been associated with a shorter time to progression (TTP) to multiple myeloma (MM). The significance of quantifying cPCs via multiparameter flow cytometry, a much more readily available diagnostic modality, in patients with SMM has not been evaluated. This study evaluated 100 patients with a known or new diagnosis of SMM who were seen at the Mayo Clinic, Rochester from January 2008 until December 2013. Patients with ≥ 150 cPCs (N = 9) were considered to have high number of cPCs based on the 97% specificity and 78% PPV of progression to MM within 2 years of cPC assessment. The median TTP of patients with ≥ 150 cPCs was 9 months compared to not reached for patients with < 150 cPCs (P < 0.001). Thus, quantification of cPCs via multiparametric flow cytometry identifies patients with SMM at very high risk of progression to MM within 2 years and warrants confirmation in larger studies. In the future, this may allow reclassification of such patients as having MM requiring therapy prior to them enduring end-organ damage.

Prognostic value of circulating plasma cells in patients with multiple myeloma: A meta-analysis

“…Whereas, several studies utilizing various methods suggested that there were small numbers of plasma cells in peripheral blood [5], namely, circulating plasma cells (CPCs), and demonstrated that it had prognostic value among MM, MGUS [6], smoldering MM [7,8] and amyloidosis [9]. However, the prognostic value of CPCs in MM remains controversial.…”

Enhancing the R‐ISS classification of newly diagnosed multiple myeloma by quantifying circulating clonal plasma cells

“…The prognostic significance of cPCs when measured by MFC has been well established across the spectrum of plasma cell disorders, such as MGUS, smoldering myeloma, MM and AL amyloidosis, at the time of diagnosis. It has also been established as a prognostic marker in MM patients undergoing ASCT by predicting for early relapse .…”

Increased circulating plasma cells detected by flow cytometry predicts poor prognosis in patients with plasma cell myeloma

“…Recent studies show a trend of using FC for cPC studies, because FC is more reproducible and sensitive than IF. SMM patients with 150 cPCs in 150,000 mononuclear cells, detected by six-color FC, showed shorter median time to progression (9 months) than those with <150 cPCs (not reached) (12). In myeloma patients, >10 cPCs among 50,000 mononuclear cells was related to shorter overall survival (10), and 400 cPCs among 150,000 mononuclear cells was associated with shorter time-to-next-treatment and overall survival (11).…”

“…The term circulating PCs (cPCs) had become interchangeable with circulating clonal PCs by previous studies, and they were known to be a marker of high risk disease (8)(9)(10)(11). SMM patients with 150 cPCs in 150,000 mononuclear cells, detected by six-color FC, showed shorter median time to progression (9 months) than those with <150 cPCs (not reached) (12). Recent studies show a trend of using FC for cPC studies, because FC is more reproducible and sensitive than IF.…”