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Heavy/Light Chain Test May Be Valuable Tool For Monitoring Multiple Myeloma

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Published: Nov 7, 2012 12:50 pm

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 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.

Photo by adobemac on Flickr – some rights reserved.
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4 Comments »

  • Gary said:

    I always get nervous when ratios are used for any test since there are always two reasons for an increase or two reasons for decrease in any ratio. One of the advantages of the free light chain test is a t 1/2 of roughly 4 hours. This makes it possible to see changes from drug therapy in days rather than weeks for an M Spike or heavy chain test. I suspect that the changes in the light chain/heavy chain ratio (or the reciprocal?) would also take weeks to detect changes. I must confess that the advantage of this test over what we already have is not obvious to me. What am I missing?

  • Susan Yagman said:

    I have Multiple Myeloma and as my treatment I have been receiving Velcade since February 2009 initially twice a week with the third week off and more recently once a week for four weeks and the fifth week off.
    The first three years my Velcade was administered via I.V. any my numbers IGG and light chains were good. Since my tumor was in and out of my bone marrow it fractured a bone near my pelvic area and I was in a wheelchair for a year and a half. Slowly with my brilliant physicians and specialists I was able to start walking again having an inch and more recently an inch and quarter wedge added to my left shoe and with two and a half years of physio therapy so now I walk “evenly”
    My question is: For the past several months I’ve been receiving Velcade sub q which in a way I am thrilled not to have the I.V.’s kill the veins in my hands but on the other hand I want to ask you if injections administered this way are as efficient as by the dreaded I.V.? I’ve had a UTI a month ago and I don’t know if it’s coincidental to this because just last week my IGG jumped from my usual 7 to 9 and last week to number 12 plus my light chain numbers were elevated then down again and recently elevated again.I was so “even-numbered” for a very long time.
    Thank you so much for your time.
    Sincerely,
    Susan Yagman

  • Amy Katz said:

    Good Afternoon-
    my husband is recently diagnosed with smoldering myeloma…….question
    blood proteins are at 3…but light chains (whatever the heck they are) went from 200 to 300 in a month…….
    should that make the prognosis worse?

    should we seek another opinion? should we seek medication therapy?

    should I be doing ANYTHING to help or just wait?

    most sincere and anxious………Amy Katz

  • Amy Katz said:

    also, my husband had a biopsy over one month ago- he is having pain and discomfort from the general area of the biopsy………

    he HONESTLY NEVER complains…………..caught him sitting on a heating pad to help relieve discomfort………..

    should it last this long????

    thanks, Amy