Participants were aged 55 years to 74 years, with a mean age of 69.1 years, and about 33% were female. Investigators collected patient data from November 1993 through December 2011, and performed their data analysis between April 2018 and December 2018, measuring levels of serum protein, serum free light chains (FLCs), and serum light chains within each immunoglobulin class.

In a cross-sectional analysis, the investigators assessed for risk factors associated with progression of MGUS to MM, based on the time point closest to MM diagnosis or selection.

They found 4 factors influencing the risk for MGUS progression:

  • Immunoglobulin isotype determined level of risk
    • Patients with the IgA isotype had a higher risk of progression to MM compared with those with the IgG isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04)
  • High concentrations of M protein increased risk
    • Individuals with an M spike concentration of at least 15 g/L were about 23 times more likely to progress to MM versus those who had M protein levels less than 15 g/L (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001)
  • Skewed serum FLC ratio affected risk
    • Participants with serum FLC ratios of less than 0.1 or more than 10 (levels which are outside of the normal range) were 46 times more likely to develop MM than those with serum FLC ratios within the normal range (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001)
  • Severity of immunoparesis impacted risk
    • Those with immunoparesis — or patients with at least 2 suppressed uninvolved immunoglobulins (IgG, IgA, and/or IgM) — were more likely to progress to MM than those without immunoparesis (adjusted OR, 19.1; 95% Cl, 7.5-48.3; 29% vs 3%; P <.001).

For those with light-chain MGUS, skewed serum FLC ratio increased risk compared with those in normal range (adjusted OR, 44.0; 95% CI, 14.2-136.3; 75% vs 6%; P <.001). In addition, immunoparesis severity increased risk compared with controls who had stable MGUS (adjusted OR, 48.6; 95% CI, 9.5-248.2; 36% vs 2%; P <.001).


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Cancer Therapy Advisor spoke with an expert in the field, Robert Kyle, MD, professor of medicine in laboratory medicine and pathology at the Mayo Clinic College of Medicine in Rochester, Minnesota, to get his read on the results. Dr Kyle said that the most intriguing finding of the study was the presence of immunoparesis as a risk factor for progression of MGUS. “Although reduction in uninvolved immunoglobulins has been recognized for years, it is reassuring to see additional evidence of its importance,” he said.

In addition, Dr Kyle noted that the finding of the serum FLC ratio as a risk factor for progression of light-chain MGUS is important. “The subset light-chain MGUS accounts for at least 20% of all patients with multiple myeloma,” he explained.

In addition to assessing for risk factors for progression, the investigators analyzed longitudinal patterns of progression to MM. To determine shifts in immune markers over time, they compared available serum samples from 159 MM cases to 156 matched controls. They found that patients who progressed to MM had significantly higher M protein spike concentrations (P =.06 for linear term and P =.02 for quadratic term), involved serum FLC levels (P =.01), and suppressed uninvolved immunoglobulins compared with controls (P  <.001).