According to a study published in JAMA Oncology, disease progression to multiple myeloma in patients with monoclonal gammopathy of undetermined significance (MGUS) can occur rapidly and was associated with immunoparesis, evolving monoclonal protein levels, and (in the case of light-chain MGUS) skewed serum free light chain ratios.

The investigators sought to longitudinally assess the association of dynamic serum immune markers in patients with stable and progressive MGUS. From 77,469 adult participants in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial ( Identifier: NCT00002540), those who had a diagnosis of progressive MGUS (187 patients) or stable MGUS (498 patients) between November 1993 and December 2011 were included in this prospective cohort study. Serially collected, prediagnostic serum samples for each participant (3266 total samples) were used to measure serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class.

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In total, 685 participants (67.3% male) with a mean age of 69.1 years were included in the study. Progressive MGUS was associated with immunoglobulin (Ig) A isotype level (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04), monoclonal spike of 15 g/L  or higher (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001), skewed (< 0.1 or > 10) serum free light chain ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001), and severe immunoparesis (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P <.001). Progressive light-chain MGUS was associated with skewed serum free light chain ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P <.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P <.001).

In the longitudinal analysis with available serial samples, 53% of the participants (23/43) who progressed to myeloma had experienced high-risk MGUS before progression, and 70% of those participants (16/23) had converted from low- or intermediate-risk to high-risk MGUS within 5 years. Similar results were observed for participants with light-chain MGUS.

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The authors concluded that “individuals with low-risk or intermediate-risk MGUS, including those with light-chain MGUS, can experience progression to high-risk MGUS multiple myeloma within 5 years” and that these dynamic risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.


1.     Landgren O, Hofmann JN, McShane CM, et al. Association of immune marker changes with progression of monoclonal gammopathy of undetermined significance to multiple myeloma [published online July 18, 2019]. JAMA Oncol. doi:10.1001/jamaoncol.2019.1568