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

Our prior studies identified the prognostic significance of quantifying cPCs by multiparametric flow cytometry (MFC) in newly diagnosed multiple myeloma (NDMM) patients. We evaluated if a similar quantification of cPCs could add prognostic value to the current R-ISS classification of 556 consecutive NDMM patients seen at the Mayo Clinic, Rochester from 2009 to 2017. Those patients that had ≥5 cPCs/μL and either R-ISS stage I or stage II disease were re-classified as R-ISS IIB stage for the purposes of this study. The median time to next therapy (TTNT) and overall survival (OS) for patients with ≥5 cPCs/μL at diagnosis was as follows: R-ISS I (N = 110) - 40 months and not reached; R-ISS II (N = 69) - 30 and 72 months; R-ISS IIB (N = 96) - 21 and 45 months and R-ISS III (N = 281) - 20 and 47 months respectively. Finally, ≥ 5 cPCs/μL retained its adverse prognostic significance in a multivariable model for TTNT and OS. Hence, quantifying cPCs by MFC can potentially enhance the R-ISS classification of a subset of NDMM patients with stage I and II disease by identifying those patients with a worse than expected survival outcome.