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What blood tests are used to track response to anti- myeloma treatment?
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• May 6, 2026
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What blood tests are used to measure myeloma and monitor response? So to give you kind of a broad overview, the observation was made in the late 1930s and 1940s that you could measure proteins that were in blood or in serum and plasma. And one of the pioneers in this area is a gentleman by the name of Jan Waldenstrom, who figured out that certain individuals seemed to have more types of proteins than others and was able to show that there actually was what was called a monoclonal antibody that is sort of an excess of a type of antibody. And so this technique was developed in the 1940s and 1950s. And then really, one of the pioneers in this research is Dr. Robert Kyle, who's still in practice at Mayo Clinic. And he was one of the very first people to figure out that a very large number of people, estimates are about 3 to 5% of the population have these monoclonal proteins in the blood. And the majority of these patients don't have, or these people, I should say, don't have myeloma. But that test became one of the cardinal ways that we figure out that people have myeloma. And basically, what you're measuring is a protein in serum, that's the kind of golden color liquid that's left over if a tube of blood clots. You run the serum over an electric gradient and it separates out proteins. And normally, people have many types of antibodies. So when you're running a serum protein electrophoresis, you can find out if people have one specific type of antibody that is a monoclonal antibody because of how it migrates on this gel. And about 80% of people with myeloma will have a serum M-spike standing for monoclonal protein spike. But more recently, it's been recognized, probably in the last maybe 30 or so years, that about 20% of people with myeloma actually have what is called light chain myeloma. And that means that they really don't usually have a spike or an M-spike that can be determined by an SPEP. They will actually have an elevation in one of two types of light chains, either kappa or lambda. Now, that used to be somewhat difficult to measure. About 20 years ago, a test was developed to actually specifically measure light chains in serum, and this is called a free light chain assay. And that's really helped us better identify that 20% of people who don't make a monoclonal protein. And then finally, there's about 1%, maybe a little bit less than 1% of people with myeloma that don't make any protein at all. So those serum tests may either not be very informative or the abnormalities may be very minimal. So they can be a little bit more challenging to diagnose. There are three ways to look at the status of a patient's myeloma, whether it's in control or not. You can do a blood test looking at your serum protein electrophoresis, and that measures your monoclonal protein, which is one way to look at the status of your myeloma. Number two is that you can look at your serum free light chains. This is also a blood test, and it looks at a different part of the antibody. It is more sensitive and less reliable than the monoclonal protein. It is a different test. And the third thing is a 24-hour urine, which I very seldom use in my myeloma patients anymore. The first two rows are the most commonly used tests to assess the status of your myeloma. So the tests that are used to follow the myeloma protein include a serum protein electrophoresis, or S-PEP, a urine protein electrophoresis, or U-PEP, which is often done on the 24-hour urine collection, as well as a test called the serum free light chain assay. And that also is another blood test that can measure levels of abnormal proteins in the blood, either the kappa or lambda light chains. In addition, there are two other tests called the serum immunofixation and urine immunofixation that also can be used, particularly when patients are getting into very deep responses, and it's difficult to measure. By the S-PEP and U-PEP, the immunofixations can often tell you if the patient still has a very low level of M protein left or if they actually may be in a complete remission, meaning you can't measure it on any of those tests that I mentioned, and their bone marrow is now negative as well. So we are usually able to follow tests in both the blood and urine to determine if patients are responding to therapy. The vast majority of myeloma patients have an abnormal protein called the monoclonal protein or M protein that can be found in their blood or in their urine at the time of diagnosis. And that M protein is a marker of their disease and allows us to follow it on a regular basis, say every few weeks, to determine if they're responding to the treatment. And so when a patient's getting a therapy regimen, typically at the beginning of every cycle of treatment, we'll repeat those myeloma tests. And if we see that the abnormal M protein is going down, then we know they're responding. If the protein is not going down or is going up, then we know that they may not be responding anymore. There are some patients who don't make a high enough level of M protein to measure in the blood or urine. And in those patients, we can follow them either by doing repeated bone marrow biopsies and trying to actually count the number of myeloma cells in the marrow. Or we may use imaging tests such as a PET CT scan or an MRI to see if their myeloma is responding to treatment. So all of these can be used in the response assessments for a patient.

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