The Reversal of Renal Impairment and its Impact on Survival in Newly Diagnosed Multiple Myeloma Patients

Abstract

Background: Proliferation rate of plasma cells (PC) is a powerful tool in evaluating all types of monoclonal gammopathies, predicting for progression as well as survival. A flow cytometry (FC)-based method to delineate the cell cycle of clonotypic PCs and determine the proportion in S-phase was developed. This method replaces a labor-intensive slide based methodology, but the prognostic power of this FC approach has not been clearly elucidated. Methods: A total of 1061 patients who had bone marrow (BM) FC PC proliferation analysis at Mayo Clinic, Rochester from May 2012 to December 2013 were studied of who 257 had relapsed disease (RMM). PC proliferation was measured by 8-color FC using antibodies to CD19, CD38, CD138, CD45, and cytoplasmic kappa and lambda Ig light chains, and DAPI DNA staining. The DNA content of the abnormal, clonotypic PCs was specifically analyzed and the %S-phase was determined by measuring the proportion of cells between G0/G1 and G2/M. Patients with inadequate plasma cells for assessment of %SP were designated as 0%. Results: The median follow up from testing for the entire cohort was 13 months (95% CI; 12.7, 13.3); 156 (15%) had died. We specifically examined the clinical features and outcomes based on two cutoffs, %SP 1 and 2. Among relapsed disease, %SP was prognostic for OS using both cutoffs (Table). In univariate analysis, %SP 2, B2microglobulin >5.5, HR FISH (t4; 14, t14;16, t14;20 & del17p) and LDH>221 were all significant, but only %SP 2 was significant in multivariable analysis. Conclusion: The %S-phase of clonal PCs determined by FC is of prognostic value in patients with RMM. This is particularly relevant because it is independent of some of the other known poor prognostic factors such as high risk FISH.