• Screening: Order with serum protein electrophoresis and immunofixation for patients suspected of having a malignant monoclonal process: multiple myeloma (MM), Waldenström macroglobulinemia, B-cell lymphoproliferative process, AL amyloidosis, monoclonal gammopathy of renal significance (MGRS). Note: this is an alternative that relieves the need for a urine immunofixation except in patients suspected of having AL amyloidosis
  • Prognosis: Use this as a baseline measurement to assess risk of all plasma cell disorders
  • Monitoring: Use to determine complete stringent remission
  • Monitoring: Order to follow patients with oligosecretory multiple myeloma and an abnormal serum free light chain ratio
  • Monitoring: Order to follow AL amyloidosis with an abnormal serum free light chain ratio
  • Note: Although the International Myeloma Working Group recommends 24-hour urine protein electrophoresis, SFLC testing has better sensitivity and prognostic value than urine measurements of the involved isotype for monitoring patients with light chain MM

Guidelines for Test Utilization

What does the test tell me?

The serum free light chain test measures the quantity of unbound immunoglobulin kappa and lambda light chain molecules in the serum. The ratio of the serum free kappa to serum free lambda is useful for detecting and following a monoclonal free light chain process. [back to top]

When should I order this test?

Features such as increased calcium, anemia, renal disease, bone pain or bone lesions that are suspicious for an underlying plasma cell disorder. The most common disorders considered are multiple myeloma, Waldenström macroglobulinemia, AL amyloidosis, plasmacytoma and monoclonal gammopathy-associated neuropathies. [back to top]

When should I NOT order this test?

This test should not be ordered unless there is a known, or suspicion of a monoclonal disorder. [back to top]

How should I interpret the result?

If the ratio of serum free kappa to serum free lambda is in the reference range established for the method and instrument used, the test does not support the presence of a monoclonal gammopathy, but it does not rule it out.

When only one of the serum free light chains is increased and the ratio of serum free kappa to serum free lambda is outside of the reference range, it is evidence supporting the presence of a monoclonal gammopathy.

When both serum free light chains are elevated and the ratio of serum free kappa to serum free lambda is either within the reference range or slightly increased, this may indicate the presence of renal disease or chronic inflammation. [back to top]

Is the test result diagnostic/confirmatory of the condition? If not, is there a diagnostic/confirmatory test?

This is not a diagnostic test. Whereas an abnormal result can support the diagnosis of a monoclonal gammopathy, demonstration of a monoclonal spike in the serum or urine by protein electrophoresis with immunochemical characterization by immunofixation, immunosubtraction or MASS-FIX is needed to provide definitive proof of the presence of a monoclonal process. [back to top]

Are there factors that can affect the lab result?

Patients with renal disease and/or chronic inflammation may have an increase in one or both of the serum free light chains that may yield a modest increase in the serum free kappa to serum free lambda ratio with some methods.

If there is a marked increase in one of the serum free light chains, this may yield a falsely low value due to a phenomenon called the high-dose hook effect, also known as antigen excess effect.

The reference range of the serum free kappa to serum free lambda ratio should be determined specifically for both the method and the instrument used for the process. The broad use of the reference range 0.26-1.65 established in 2002 is no longer appropriate. [back to top]

Are there considerations for special populations?

Monoclonal gammopathies are rare in children; their occurrence gradually increases with age. [back to top]

What other test(s) might be indicated?

This test is usually performed together with serum protein electrophoresis, immunofixation and quantification of total IgG, IgA and IgM. Immunosubtraction or MASS-FIX are alternatives to immunofixation. [back to top]

References

Abadie JM et al. Clin Chem 131:166, 2009.

Cotten SW Clin Biochem 58:100, 2018.

Dejoie T et al. Blood 128:2941, 2016 doi: 10.1182/blood-2016-07-726778

Dimopoulos MA, et al. Lancet Oncol 24:e293, 2023l doi: 10.1016/S1470-2045(23)00223-1.

Dispenzieri A, et al. Leukemia 23;215, 2009.

Graziani MS and Merlini G. Expert Rev Mol Diag 14;55, 2014.

Genzen JR, et al. Arch Pathol Lab Med doi: 10.5858/1401.2017-0128-CP

Keren DF et al. Arch Pathol 146:575, 2022 doi: 10.5858/arpa.2020-0794-CP

Khoriaty R et al. Clin Lymphoma Myeloma Leuk 10:E10-E13, 2010

Larson D, et al. NEJM (letter) 367:581, 2012

Leung N, et al. Nat Rev Nephrol 15:45, 2019

Long TE, et al. Blood Cancer J 12:133, 2022

Kumar SK, et al. Mayo Clin Proc 79:867, 2004.

Rajkumar SF et al. Lancet Oncol 15;e538, 2014.

Schroeder LF et al. Clin Biochem doi:10.1016/j.clinbiochem.2023.110604, 2023

Singh G. Am J Clin Pathol 146:207, 2016.

Treger RS. Am J Clin Pathol doi: 10.1093/ajcp/aqad137, 2023  

Last reviewed: February 2024. The content for Optimal Testing: the Association for Diagnostics & Laboratory Medicine’s (ADLM) Guide to Lab Test Utilization has been developed and approved by the the Academy of Diagnostics & Laboratory Medicine and ADLM’s Science and Practice Core Committee.

As the fields of laboratory medicine and diagnostic testing continue to grow at an incredible rate, the knowledge and expertise of clinical laboratory professionals is essential to ensure that patients received the highest quality and most useful laboratory tests. ADLM’s Academy and Science and Practice Core Committee have developed a test utilization resource focusing on commonly misused tests in hospitals and clinics. Improper test utilization can result in poor patient outcomes and waste in the healthcare system. This important resource geared toward medical professionals recommends better tests and diagnostic practices. Always consult your laboratory director to make sure these recommendations are appropriate for your patient population.