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Light-chain monoclonal gammopathy of undetermined significance (LC MGUS) is a form of MGUS characterized by an abnormal free light-chain (FLC) ratio with elevated serum free kappa and lambda light chains. The current definition for LC MGUS is based on a small cohort (n = 282) of healthy individuals. It has since been developed for individuals with impaired kidney function, but not those with preserved kidney function.1
During the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, Einarsson Long presented results from the iStopMM study (NCT03327597), highlighting a novel definition for LC MGUS based on serum FLC measurements in individuals with normal kidney function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2).
The overall trial design of the iStopMM study has been previously outlined by the Multiple Myeloma Hub.
The standard definition for LC MGUS in patients with preserved kidney function is:
This analysis aimed to redefine the reference intervals for individuals with preserved kidney function, to limit overdiagnosis of LC MGUS. Overall,
Table 1. Revised intervals by age*
Reference intervals, mg/L (unless otherwise specified) |
Age <70 years |
Age >70 years |
---|---|---|
Kappa |
6.3–39.0 |
7.0–55.8 |
Lambda |
5.9–36.7 |
6.4–48.0 |
FLC, ratio |
0.44–2.16 |
0.46–2.59 |
FLC, free light chain. |
An outline of the revised definition for LC MGUS is shown in Figure 1.
Figure 1. Revised definition of LC MGUS*
eGFR, estimated glomerular filtration rate; FLC, free-light chain; LC MGUS, light-chain monoclonal gammopathy of undetermined significance.
*Adapted from Einarsson Long.1
Previously, the standard reference intervals for LC MGUS diagnosis were based on a small cohort of patients and lead to inaccurate thresholds, especially for younger individuals. This revised definition of LC MGUS, based on the iStopMM study, demonstrated significantly lower rates of false positive diagnoses, which could reduce unnecessary health anxiety in patients and aid in the provision of healthcare resources.
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