An Untrustworthy Myeloma Assay?
Gurmukh Singh warns of inaccuracies in the serum free light chain assay
Even for blood cancers, the answer to diagnostic puzzles can be hidden elsewhere. Myeloma, a cancer of the plasma cells, is one such example. The serum free light chain assay (SFLCA) has a one-in-four chance of missing the signs of disease; other assays – such as serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) – are more reliable, but equally invasive. Plus, they are less likely to be ordered if clinicians have faith in the newer SFLCA test. The solution? A simple, noninvasive legacy test that examines the urine for signs of disease.
Gurmukh Singh, Vice Chair of Clinical Affairs for the Department of Pathology at the Medical College of Georgia at Augusta University, explains: “During regular examinations of the data generally used in diagnosis and monitoring of multiple myeloma (and other monoclonal gammopathies) from patients being treated at Medical College of Georgia, I noticed disparities in the findings from protein electrophoresis results and SFLCA.” The International Myeloma Working Group recognizes SPEP and SIFE as the gold standards for diagnosing myeloma, so the discrepancies between those tests and the SFLCA results prompted Singh and his colleagues to perform a retrospective analysis of the data (1).
Singh warns that SFLCA assay results are unreliable for diagnosis of myeloma and other monoclonal gammopathies. “In patients without monoclonal gammopathies, about 36 percent have an abnormal SFLCA result – and about 30 percent of patients with myeloma have a normal SFLCA.” This false negative rate is even higher in lambda chain-associated myelomas and monoclonal gammopathies. “The need for a normal kappa/lambda ratio to qualify for stringent complete response introduces errors due to the frequent occurrence of oligoclonal patterns in patients treated with stem cell transplantation,” Singh says. “The oligoclonal pattern often produces a false-positive, kappa-dominant abnormal kappa/lambda ratio.”
He and his colleagues believe that the marked disparities in the SFLCA results in intact immunoglobulin myelomas warrant a re-examination of the criteria for definitive diagnosis of myeloma. Fortunately, noninvasive diagnostic options remain; Singh – an enthusiastic advocate for clinically useful tests and the curtailing of less-than-useful ones – has proposed that all SPEP orders at his institution also receive urine protein electrophoresis and immunoelectrophoresis (UPEP/UIFE) testing.
- WS Lee, G Singh, “Serum free light chains in neoplastic monoclonal gammopathies: relative under-detection of lambda dominant kappa/lambda ratio, and underproduction of free lambda light chains, as compared to kappa light chains, in patients with neoplastic monoclonal gammopathies”, J Clin Med Res, 10, 562–569 (2018). PMID: 29904440.