Re: Presenting Signs of Multiple Myeloma and the Effect of Diagnostic Delay on the Prognosis

To the Editor: The article by Goldshmidt et al¹ addresses an important issue of the impact of early diagnosis in the outcome of patients with multiple myeloma. The authors mention that some have advocated use of serum-free light-chain assay (SFLCA) for “screening.” SFLCA has been promoted for diagnosing, determining the prognosis, and monitoring of monoclonal gammopathies.² However, empirical evidence suggests a far more limited role for SFLCA. Serum protein electrophoresis and serum immunofixation electrophoresis are the gold standards for diagnosis;³ these two alone are sufficient to diagnose about 95% cases. Patients with light-chain gammopathy can be detected by urine protein electrophoresis and urine immunofixation electrophoresis.

Among patients without monoclonal gammopathy, the κ-to-λ ratio is abnormal in >35%, and the false-positive rate is about 55% in patients with polyclonal hypergammaglobulinemia.⁴ In monoclonal gammopathy there is an overall 27% false-negative κ-to-λ ratio. The false-negative rate is up to 67% for patients with monoclonal gammopathy of undetermined significance.⁵ SFLCA and κ-to-λ ratio have virtually no role in the diagnosis of monoclonal gammopathy, as an abnormal κ-to-λ ratio is not diagnostic of monoclonal gammopathy and a normal κ-to-λ ratio does not exclude monoclonal gammopathy.⁶