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Prashant Kapoor, MD, FACP


Can Revised FLC Reference Intervals Improve Diagnosis of Light Chain MGUS?

By: Joshua D. Madera, MD
Posted: Monday, January 8, 2024

The number of serum-free light chains (FLC) and the ratio of free kappa to free lambda light chains have been used to diagnose, risk stratify, and manage various plasma cell disorders. According to the results of the iStopMM study, presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 535), the standard reference intervals that have been employed appear to be inaccurate for individuals with preserved renal function. Based on their findings, Thorir Einarsson Long, MD, PhD, of the University of Iceland, Reykjavik, and colleagues recommend modifying the reference intervals to decrease the rate of false-positive diagnoses of light chain monoclonal gammopathy of undetermined significance (LC-MGUS).

Clinical data from 41,882 patients with normal renal function were collected from the Istopmm study. These patients were selected after undergoing screening for MGUS based on the results from serum electrophoresis, immunofixation, and serum FLC assay. Serum creatinine values were used to identify each individual’s estimated glomerular filtration rate.

The study results revealed the median serum-free kappa, serum-free lambda, and FLC ratio as 14.3, 14.2, and 1.02, respectively. Strong correlations were identified between an individual’s age and the FLC ratio (correlation coefficient = 0.16), the number of serum kappa FLC (correlation coefficient = 0.27), and the number of serum lambda FLC (correlation coefficient = 0.14). When compared with the standard reference intervals, abnormal results were revealed for 17.5% of serum kappa, 3.9% of serum lambda, and 4.5% of FLC ratio values. Moreover, based on the FLC ratio, the prevalence of LC-MGUS was 2.0%.

“Based on these findings, we established new reference intervals for serum kappa and lambda FLC and FLC ratio, partitioned by age less than 70 years and greater than or equal to 70 years,” explained Dr. Long and colleagues.

Disclosure: Dr. Einarsson reported no conflicts of interest. For full disclosures of the other study authors, visit

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