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

Abstract

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.

FIGURE 1:

Levels of cPCs detected based on the primary molecular cytogenetics at the time of diagnosis: A) the levels of cPCs/150,000 events analyzed between hyperdiploid vs. sub-types of non-hyperdiploid, B) the absolute number of cPCs/μL between hyperdiploid vs. sub-types of non-hyperdiploid. (****, Mann Whitney = P < 0.001)

FIGURE 1:

Levels of cPCs detected based on the primary molecular cytogenetics at the time of diagnosis: A) the levels of cPCs/150,000 events analyzed between hyperdiploid vs. sub-types of non-hyperdiploid, B) the absolute number of cPCs/μL between hyperdiploid vs. sub-types of non-hyperdiploid. (****, Mann Whitney = P < 0.001)

FIGURE 2:

Kapan Meir curves comparing the (A) TTNT and (B) OS for patients based on the absolute number of cPCs/μL.

FIGURE 2:

Kapan Meir curves comparing the (A) TTNT and (B) OS for patients based on the absolute number of cPCs/μL.

FIGURE 3:

Distribution of patients based on ISS, R-ISS and mR-ISS classification schemes. (* results are the same using either cutoffs by cPCs/150,000 events analyzed or absolute number of cPCs/μL).

FIGURE 4:

Kapan Meir curves comparing the (A) TTNT and (B) OS for patients with a mR-ISS classification based on the absolute number of cPCs/μL.

FIGURE 4:

Kapan Meir curves comparing the (A) TTNT and (B) OS for patients with a mR-ISS classification based on the absolute number of cPCs/μL.