Results of a recent retrospective analysis show that the heavy/light chain test has high potential as a tool for the detection of abnormal monoclonal protein, the evaluation of response to therapy, and as a prognostic marker in multiple myeloma patients.

The heavy/light chain test was more sensitive to low levels of monoclonal (M)-protein compared to conventional detection methods. Thus, the study investigators conclude that the test may become valuable in confirming and quantifying M-protein levels, measuring patient responses to treatment, detecting early signs of relapse, and identifying residual disease in multiple myeloma patients.

However, the investigators point out that further prospective studies are needed to confirm their findings.

Plasma cells produce a variety of proteins called immunoglobulins that help fight infections. Each immunoglobulin is made up of two identical heavy chains and two identical light chains. There are five different types of heavy chains, including IgG, IgA, IgM, IgD, and IgE. Furthermore, there are two types of light chains, called kappa and lambda.

Each plasma cell will produce one type of immunoglobulin. Normally, people have many types of plasma cells and therefore a variety of immunoglobulins.  However, multiple myeloma patients overproduce a single type of plasma cell.  This leads to the overproduction of one immunoglobulin, also called M-protein, which accumulates in the blood.

Serum protein electrophoresis is a conventional diagnostic tool for multiple myeloma. This test measures protein levels in the blood. However, according to the study investigators, its effectiveness is limited when M-proteins are present in low concentrations.

Another tool used in the diagnosis and post-treatment evaluation of myeloma patients is the free light chain assay, which measures the amount of free light chains in the blood.

The current study focused on the heavy/light chain test, a relatively new test which allows researchers to calculate the ratio of each heavy chain and light chain pair in multiple myeloma patients. Prior studies have shown that heavy/light chain ratios may be useful in screening, monitoring, and risk stratification of patients (see, for example, this recent Beacon ^[1] news article).

The goal of the current study was to compare protein measurements obtained from the heavy/light chain test and conventional methods including serum protein electrophoresis and the free light chain assay. The study investigators also evaluated the heavy/light chain ratio as a potential prognostic tool for newly diagnosed multiple myeloma patients.

The researchers retrospectively evaluated records of 156 newly diagnosed multiple myeloma patients who had received their first line of therapy. The median age of the patients was 66 years; 64 percent of patients had IgG myeloma, and 34 percent had IgA myeloma.

The median follow-up time was 46 months.

The serum protein electrophoresis test was unable to measure M-protein levels in 46 percent of patients with IgA myeloma and 4 percent of patients with IgG myeloma. The heavy/light chain test, however, was able to determine protein measurements for all patients.

Following initial therapy, the overall response rate was 75 percent. Specifically, 21 percent of patients achieved a complete response, 11 percent achieved a near complete response, 12 percent reached a very good partial response, and 31 percent reached a partial response.

Compared to conventional methods, the heavy/light chain test had a higher sensitivity in the detection of residual disease. An abnormal heavy/light chain ratio was found in 26 percent of patients with a complete response; half of these patients also had  abnormal free light chain ratios.

According to the researchers, patients switching from normal to abnormal heavy/light chain ratios was indicative of impending relapse up to months before patients showed conventional clinical signs of relapse.

The researchers also found a link between heavy/light chain ratios and patient survival.

The median overall survival was 54 months for all patients included in the analysis. At the time of best response, patients with abnormal heavy/light chain ratios had significantly shorter overall survival (41 months) than those with normal heavy/light chain ratios (median not yet reached).

For more information, please see the study in the journal Leukemia ^[2].