Enumeration and characterization of circulating multiple myeloma cells in patients with plasma cell disorders

Br J Haematol. 2018 Jan;180(1):71-81. doi: 10.1111/bjh.15003. Epub 2017 Nov 5.

Abstract

We have developed an automated assay to enumerate and characterize circulating multiple myeloma cells (CMMC) from peripheral blood of patients with plasma cell disorders. CMMC show expression of genes characteristic of myeloma and fluorescence in situ hybridisation results on CMMC correlated well with bone marrow results. We enumerated CMMC from over 1000 patient samples including separate cohorts of newly diagnosed multiple myeloma and high/intermediate risk smouldering multiple myeloma (SMM) with clinical follow-up data. In newly diagnosed myeloma patient samples, CMMC counts correlated with other clinical measures of disease burden, including the percentage of bone marrow plasma cells, serum M protein, and International Staging System stage. CMMC counts decreased significantly from baseline when a remission was achieved due to treatment (P < 0·001). Patients with CMMC counts ≥100 at remission showed reduced survival relative to patients with CMMC counts <100. Patients with undetectable CMMC in remission showed further overall survival benefits. In the SMM cohort, there was a trend toward higher CMMC in patients with higher-risk myeloma precursor states. Significantly higher CMMC counts were observed between intermediate/high risk SMM patients that progressed versus those without progression (P = 0·031). CMMC allow a non-invasive means of monitoring tumour biology and may have use as a prognostic test for patients with plasma cell disorders.

Keywords: biomarker; circulating tumour cell; multiple myeloma; plasma cell; smouldering myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / pathology
  • Cell Count*
  • Cohort Studies
  • Diagnosis, Differential
  • Female
  • Flow Cytometry / methods
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / genetics
  • Multiple Myeloma / mortality
  • Neoplasms, Plasma Cell / blood
  • Neoplasms, Plasma Cell / diagnosis*
  • Neoplasms, Plasma Cell / genetics
  • Neoplasms, Plasma Cell / mortality
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology*
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Sensitivity and Specificity