Augusta University
Won Sok Lee (left) and Gurmukh Singh Photo by Phil Jones,
Researchers are questioning the clinical usefulness of the serum free light chain assay (SFLCA) for patients with monoclonal gammopathies.
The investigators found evidence suggesting that, about 25% of the time, SFLCA provides a negative κ/λ ratio in patients with lambda chain monoclonal gammopathies who have free homogenous lambda light chains detectable in their urine.
“If you have a lambda chain-associated lesion and you don’t do a urine study—just rely on the serum free light chain assay—about 1 out of 4 times, the assay will tell you that you don’t have anything when you actually do,” explained Won Sok Lee, MD, of the Medical College of Georgia at Augusta University.
“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” said Gurmukh Singh, MD, PhD, also of the Medical College of Georgia.
Drs Singh and Lee made this recommendation and detailed the supporting research in the Journal of Clinical Medicine Research.
The researchers evaluated results of serum and urine tests in 175 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple/plasma cell myeloma (MM).
In addition to results of SFLCA, the investigators looked at results of serum protein electrophoresis, serum protein immunofixation electrophoresis, urine protein electrophoresis, and urine protein immunofixation electrophoresis.
This analysis revealed “systematic under-detection” of serum free lambda light chains by SFLCA as well as an under-detection of the lambda-dominant ratio.
The researchers integrated the results of this study with findings from an earlier study* and concluded that, as compared to kappa chain lesions:
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MGUS is 29%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in MM is 32%
- The excess false-negative rate of κ/λ ratio for lambda chain lesions in all neoplastic monoclonal gammopathies (MGUS, MM, and SMM) is approximately 30%.
The investigators said they believe that 5% of the 30% false-negative rate is a result of under-production of excess free lambda light chains, and about 25% could be due to under-detection of monoclonal lambda light chains by SFLCA.
“[A patient] may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don’t make that many excess abnormal proteins,” Dr Singh said.
However, Drs Singh and Lee also said it’s possible that unknown factors, such as general over-production of polyclonal kappa light chains in tertiary care patients, may alter the κ/λ ratio.
*Singh, G. Serum Free Light Chain Assay and κ/λ Ratio: Performance in Patients With Monoclonal Gammopathy-High False Negative Rate for κ/λ Ratio. J Clin Med Res. 2017 Jan; 9(1): 46–57.