Urine Tests May Be Better Than Serum for Multiple Myeloma Screening, Study Suggests

Urine tests may be better than serum tests to diagnose multiple myeloma or its precursor conditions, because they can spot cases that would be missed by serum screenings, a study has found.

Serum free light chain tests may fail to diagnose about 25 percent of the people with multiple myeloma or the conditions that may precede it, the researchers report.

The study, “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,” was published in the Journal of Clinical Medicine Research.

One of the most frequently used tests for diagnosing multiple myeloma is serum free light chain assays, which looks for the excessive production of antibodies, or immunoglobulins, in the blood.

In people with tumors in their plasma cells — the immune cells responsible for producing antibodies — these cells start making too much of a single and abnormal type of immunoglobulin, particularly one of its portions called the light chain.

Plasma cell tumors comprise several conditions called neoplastic monoclonal gammopathies (NMGs) including, by order of severity, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and multiple myeloma.

To screen for these tumors, the higher-than-normal free light chains can be quantified in serum and urine. However, in recent years, serum assays have gradually replaced urine tests, because physicians believed them to be redundant.

Now researchers have found that urine screenings may still be useful because they are able to identify cases of multiple myeloma and other NMGs that would be missed by serum assays.

“When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells,” Gurmukh Singh, MD, PhD, vice chair of clinical affairs for the department of pathology at the Medical College of Georgia at Augusta University and senior author of the study, said in a press release.

Researchers reviewed past urine and serum tests of 175 patients diagnosed with an NMG, including multiple myeloma.

They saw that patients whose plasma cell tumors produced an abnormal type of light chain, called lambda, were often undiagnosed.

Immunoglobulin light chains come in two different types, kappa and lambda. Humans normally produce about double the amount of kappa light chains, but cancer can affect both light chains.

In people with lambda chain tumors, it’s expected that the lambda/kappa ratio gets higher. However, in some patients, this ratio remains normal in the serum, while abnormal levels were showing up in the urine.

These ratios were frequently abnormal among patients with kappa chain lesions, but remained normal on serum tests in about 25% of patients with lambda chain lesions. Importantly, this imbalance in lambda chain production was detectable in urine tests.

Researchers estimate that out of the total 30% false negative rate — the proportion of patients that failed to be diagnosed — by the serum test, about 25% are due to under-detection by the serum test. The remaining 5% are patients whose tumors produce very little lambda light chains.

Conversely, serum tests show a high rate of false positives — patients misdiagnosed as having a tumor. The light chain ratio can look abnormal in the serum of nearly 36% of individuals with no signs of NMGs.

“The results question the medical necessity and clinical usefulness of the serum free light chain assay,” the researchers wrote.

“UPEP [urine protein electrophoresis test] is grossly underutilized in investigation of monoclonal gammopathies,” they said. Although more expensive, the results suggest the urine test is a better diagnostic tool for patients with plasma cell tumors.