Comparative evaluation of involved free light chain and monoclonal spike as markers for progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder, with a 1% yearly risk of progression to multiple myeloma (MM). Evolution of M-spike and serum free light chain (sFLC) during follow-up could identify patients at high risk of progression. In this region-wide study, including 4756 individuals, 987 patients with MGUS were identified, and baseline factors as well as evolving involved FLC (iFLC) were evaluated as potential markers for risk of progression from MGUS to MM. Furthermore, evolving iFLC and M-spike were assessed quarterly for a median of 5 years. At baseline, patients that progressed had significantly higher iFLC compared to non-progressors. The risk factors of M-spike >1.5 g/dL, age >65 years and iFLC >100 mg/L were all independently associated with increased risk of MGUS to MM progression. For patients that had any two or three risk factors, the 5-year cumulative probability of progression was significantly higher (31%) compared to no risk factors (2%). Evolving iFLC >100 mg/L during follow-up was consistently associated with increased risk of progression. Based on our observations, we propose to include iFLC as a monitoring tool for all MGUS patients. Furthermore, we recommend a quarterly monitoring in all high-risk patients. Finally, we suggest that the risk of MGUS progression should be stratified with age, M-spike, and iFLC at baseline.

FIGURE 1

Impact of risk factors (RFs) on cumulative probability of progression from MGUS to MM. Probabilities were compared by log‐rank tests and is presented between groups. Absence of any risk factors were labeled as low risk (n = 301, 30%). Presence of only one RF, regardless of which, were labeled as intermediate risk (n = 585, 59%). Presence of any two, regardless of which, or all three RFs, were labeled as high risk (n = 101, 10%). Numbers below the graph indicate the number of patients within each risk group left at each time point. Significant differences of probabilities were observed between low risk and intermediate risk (P < .001), between low risk and intermediate risk (P < .001) and between intermediate and high risk (P < .001)

FIGURE 2

Risk of progression of MGUS to MM by evolving iFLC and M‐spike in plasma over 10 years of follow‐up. The Cox regression hazard ratios with the 95% confidence interval per 3 months’ time are plotted per graph. The black line represents HR, the gray area the 95% confidence interval, and the red line represents HR = 1. A, Absolute increase of 0.5 g/dL of serum M‐spike from baseline value. B, Absolute increase of 100 mg/L of plasma iFLC from baseline value. C, Increase in serum M‐spike >0.5 g/dL at any time during follow‐up regardless of baseline value. D, Increase in serum iFLC >100 mg/L at any time during follow‐up regardless of baseline value