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What Tests Are Used to Evaluate Myeloma Patients?

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Published on April 4, 2019

What are doctors testing for in multiple myeloma patients? How is treatment response monitored? Renowned myeloma expert Dr. Elisabet Manasanch, from The University of Texas MD Anderson Cancer Center, gives an in-depth look at different types of modern tests used for myeloma and explains what the results reveal about a person’s condition. Watch now to find out more.

This is a Patient Empowerment Network program produced by Patient Power in partnership with The University of Texas MD Anderson Cancer Center. We thank AbbVie, Inc., Celgene Corporation, and Sanofi for their support.

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Transcript | What Tests Are Used to Evaluate Myeloma Patients?

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That's how you’ll get care that's most appropriate for you.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

Andrew Schorr:                     

Now, doctor, let me ask you this. So, here’s the thing. You’ve got all of these variables. So, it sounds like the testing is one indication.

But what are the other things you’re looking at? It seems almost like a constellation for you, as a practitioner, to know how is somebody doing. Or even, if you’ve had a certain treatment, how is that treatment going. So, tell us what else you look at. So, the MRD testing to the 10 to the whatever, 5 or 6, as you can, what else? How do you assess how somebody is doing?

Dr. Manasanch:          

Well, so, the first things that we do is we have what we call our myeloma labs. And the myeloma labs include something called electrophoresis. That’s a test that looks at each patient’s individual paraproteins. Those are the proteins that the myeloma makes. So, most myelomas, about 80 percent to 85 percent make what we call—they make an immunoglobulin. And those immunoglobulins, they actually have two parts. They have a heavy chain and a light chain. 

That’s how immunoglobulins are structured. And those immunoglobulins usually fight infections. But the immunoglobulin that the myeloma cells make does not fight any infection. In fact, I’m just going to go in there and say that we have some exciting research here where we’re going to be looking at whether these paraproteins target in myeloma. So, we don’t know what they target. In a healthy patient, an immunoglobulin is supposed to target an infection or something that is foreign to us. And, usually, it’s viruses, bacteria, and so on. 

But in myeloma patients, we don’t know. And we’re trying to look into that to see what is going to happen with the etiology of myeloma. Now, that’s what we look at in the blood, so those immunoglobins, those paraproteins. About 10 percent or 15 percent of patients, they don’t have the heavy chain. So, they have only one part or two parts of the structure of immunoglobulin. Instead of having the heavy chain and the light chain, in the immunoglobulin, they just have the light chain. 

So, when I say this, it may sound a little complicated, but it’s really very easy. Most myeloma patients, they have an immunoglobulin G. So, we look to see how much of the immunoglobulin G is in the blood. Some patients will have immunoglobulin A, some will have immunoglobulin M. Maybe one percent of patients will have immunoglobulin E or an immunoglobulin D as in David. Those are very rare, but we see them. So, that’s usually most patients, myeloma express some of those. So, that’s a nice way you can correlate how much tumor you have, how much myeloma you have, by how much of this protein is in the blood. 

Usually, most of the time, you can correlate that pretty well. So, the higher the level is in the bone marrow, the higher it is also in the blood. And so, usually, with a simple blood test, you can already know a lot about the patient’s myeloma, if the levels are very high or not. So, the first thing we look at, again, is this electrophoresis.

And that tells us how much of those immunoglobulin are in the blood. And then, we have, also, the light chains, which are kappa and lambda. So, we look at those. Those are the second part of the immunoglobulin. And, again, about 15 percent of the patients, they don’t have the heavy chain. They don’t have the immunoglobulin G or D or M. They just have the light chain, kappa or lambda. So, patients that have the whole protein, the whole paraprotein, the whole immunoglobulin, both the heavy part and the light chain part, we look at that through electrophoresis. And that’s very useful. And that’s how we determine the response. 

So, you have the patient that has an immunoglobulin G kappa myeloma, that’s what the myeloma is making. And they start with a number of four. So, even if that number goes from 4 to 2, that’s a partial response. If it goes from 2 to 0.4, that’s a very good partial response. 

And if it goes to 0 that could be a complete remission. So, really, most of what you need to measure like partial response, very good partial response, is really just the paraprotein. If you have a light chain myeloma, then, you have to look at the light chains in the blood. So, you don’t look so much at this paraprotein and the electrophoresis, but you look at the light chains. So, basically, you need, for someone who has the regular myeloma like most people have that has both heavy and light chain, you just look at the electrophoresis. And that can tell you a lot already. And that’s just one test. 

Then, if you want to know about complete remission, once you reach that zero, then, you have to look at something called immunofixation that tells you the type of paraprotein. You have to look at the light chains. Also, you have to look at the variations in the light chains in the blood. And you have to look also at the urine. So, usually, that’s what we do with each patient.

So, there are a lot of tests involved in this. So, the urine, the best test to measure the urine, in myeloma, is still a 24-hour urine that measures how much of the Bence Jones protein, which is the myeloma protein in the urine, varies. And that can be done quite easily, although it’s a little bit cumbersome for patients. And you look at that. So, only once you reach your complete remission, once the numbers in the blood are negative, the numbers in the urine are negative, then, usually, that’s when we say, okay, we’re going to do a bone marrow biopsy. 

And then, if the bone marrow biopsy is negative, the bone marrow is normal, then, you can do your MRD testing, your minimal residual disease testing. And that’s how the levels of remission. However, it gets a little bit tricky because you can have a patient that has still some paraprotein in the blood. So, the blood markers are positive. The urine markers are positive. And then, you do your bone marrow, and you do your minimal residual disease testing, and that is still showing a little bit of the – sorry, that is, basically, negative.

So, you can have an MRD-negative test. And you can have patients having some paraprotein in their blood. Okay. The main explanation for this is because the paraproteins, the IgG kappa mainly, takes a very long time to disappear from the blood. So, you may actually be looking at the bone marrow, and you don’t see any myeloma in the bone marrow, and that’s actually a good thing. What it likely means, for most patients, is that, with time, what they’re seeing in the blood will go away. So, it does seem that the IgG kappa tends to linger in the blood. 

So, if you have patients here that have IgG kappa, and they have a minimal residual disease testing in the bone marrow, and that is not normal, and they still have a little bit of their IGG kappa in the blood, then, it is likely that this will actually go away with time. 

Whereas, if the MRD testing is positive, it is a little bit more difficult. So, it can give you chances. But, basically, there are a lot of tests that we use.

Andrew Schorr:          

Wow. So, I want to say, first of all, thank you for that because ladies and gentlemen watching are living with myeloma. Now, you hear how complicated this is to really understand, maybe not for Dr. Manasanch, but for some, particularly community oncologists around the country, around the world, to really help you get a clear picture of what’s going on with you. And this whole thing about lingering of some of these paraproteins where you’ve had an MRD-negative test, I’d say, oh, I have an MRD-negative test. And then, if this other one came up, I’d say, oh, my God, could you explain the linger. And it’s maybe not such a big deal, right?

Dr. Manasanch:          

It doesn’t have to be a big deal. And, usually, it still is a good thing, if you have still a little bit of protein in the blood and they myeloma.

And then, the bone marrow is normal, and the flow MRD or the clonoSEQ is negative that usually, probably, means that it’s just taking you a little bit longer to clear that protein from the blood.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.