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What Are the Precursor Conditions to Multiple Myeloma?

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Published on May 21, 2021

Multiple Myeloma Precursor Conditions Explained

In this excerpt from our recent Dinner with the Docs program, hosted in partnership with Rocky Mountain Cancer Centers (RMCC), host and patient advocate Cindy Chmielewski talks to two experts about the precursor conditions to multiple myeloma, what defines them, how they're monitored, and when they need to be treated now and in the future. John M. Burke, MD, is a Medical Oncologist/Hematologist at Rocky Mountain Cancer Centers (Aurora, Centennial, Littleton, Swedish). Tara Gregory, MD, is a Medical Oncologist/Transplant and Cellular Therapies Specialist at the Colorado Blood Cancer Institute. Keep watching to learn more.

Support for this series has been provided by Karyopharm Therapeutics. Patient Power maintains complete editorial control and is solely responsible for program content.


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Transcript | What Are the Precursor Conditions to Multiple Myeloma?

Cindy Chmielewski: And Dr. Burke, can you start off by telling us what is multiple myeloma?

What Is the Biology of Multiple Myeloma?

Dr. Burke: Sure. Yeah, it's a cancer of a cell type that's called plasma cells. Plasma cells have, really, one main job in life, which is to manufacture antibodies. I think most of us have heard of antibodies, which are proteins that are part of our immune system. And so plasma cells manufacture these antibodies. And what happens is that a plasma cell can turn into a cancer cell, meaning that it clones itself more frequently than it should, makes other copies of itself and it fails to die like it should. Cells are like all of us, they're supposed to have a lifespan. They're born, they do their thing for a while, and then they reproduce, and they die off.

Well, these guys are not dying, these plasma cells. And so over time, that combination of cells failing to die and then reproducing themselves too quickly, the clone of plasma cells accumulates in a person's body. So you get way too many of the identical plasma cells all making the same antibody protein. And that process is caused by mutations of genes inside the plasma cells and the accumulation of plasma cells and the things that they produce are what lead to the consequences that we see in patients with multiple myeloma.

Cindy Chmielewski: Right. I guess it's not too good to have too many of the same kinds of plasma cell, we need many different kinds to fight off all the things in our body.

Dr. Burke: You got it. Yeah, because you can imagine with all the viruses and bacteria and all of the proteins that they all have, our immune systems need to be highly varied, and to be able to respond to millions and millions and millions of these different foreign invaders that can get into us. And so, one plasma cell, that's all a clone and all making the same antibody, has virtually no benefit to your immune system. In fact, it leads to harm to your immune system because all the other plasma cells and the antibody levels become reduced. And so in patients with myeloma, one of the features of it is lowering of their normal antibody levels and suppression of their immune system. So, kind of paradoxically, you have all these plasma cells with myeloma, but your immune system is worse.

What Are Precursor Conditions? Do They Determine Multiple Myeloma Risk?

Cindy Chmielewski: Okay, great. And Dr. Gregory, can you talk about the precursor conditions? What does precursor mean, and what are they?

Dr. Gregory: Sure. That's a great question. So everybody with myeloma had something else first and that something else, where just like Dr. Burke was pointing out these funny plasma cells that aren't doing the right thing. But if there aren't too many of them and they're not making too much protein, then that's typically what we call a precursor condition. So, the one precursor condition that we talk about is monoclonal gammopathy of undetermined significance (MGUS), which is a really fancy term for you have a protein in your blood and we don't know if it's ever going to matter or not. So what that typically means is that you have less than 10% of those bad plasma cells that Dr. Burke was pointing out and the protein that they make, which we refer to as a monoclonal spike, or the M spike is less than three grams per deciliter. You're not having repeated infections. You're not breaking bones. Your kidneys are healthy.

And what we can do when somebody has MGUS, or what we call it, our abbreviation MGUS, is that we can look at some of those levels of your protein and predict, okay in 20 years, what's the chance that we think you might have myeloma? A second precursor condition is what we call asymptomatic or smoldering myeloma. So, it means that you hit one of those tick marks for multiple myeloma, meaning you had over 10% or more plasma cells in the bone marrow, or that protein level was three or more, but it's not enough disease to make us want to treat you and you don't have any problems. So, we call that smoldering and we have risk factors that we can look at for people as well to predict how long do we think it's going to be until you need treatment.

Cindy Chmielewski: And with these precursor conditions, what kind of monitoring happens in MGUS and smoldering myeloma?

How Are Precursor Conditions Monitored?

Dr. Gregory: Well, what's been really exciting is that we've been getting more and more data published within the last five years, helping us to know exactly the answer to that question. So if we have someone with what we consider a low risk monoclonal gammopathy of undetermined significance, that's a patient who probably never needs a bone marrow biopsy. And really the recommendations vary based on the U.S., the different organizations and in Europe. Some people will say, never need to check it again. Some people say, check it out in two to three years. Some of the recommendations say, check it in six months and if it's the same, don't bother. And then as the risk factors go up, then we escalate our recommendations to checking those proteins and scans about every three to six months.

Cindy Chmielewski: Okay. So, if you're diagnosed with smoldering myeloma, what kind of… should you have imaging at the time of diagnosis of smoldering myeloma?

Dr. Gregory: That's a great question. So, when you're diagnosed with myeloma, we have to have imaging so that we know, do you have a problem with your bones, which means we should treat you because you have a symptom, or can we leave you alone and are you truly smoldering? Meaning your myeloma hasn't caused you a problem. And what's also happened in the last six years is about six years ago. Gosh, it might even be seven, I can't believe these years are floating by so fast. But we said it's not enough just to have x-rays and we need to do something called advanced bone imaging. So, we have the International Myeloma Working Group recommendations that came out in 2014. And those said that skeletal survey is not enough, advanced bone imaging, and that could be one of three things. That could be an MRI skeletal survey. You have to have a specialized set on the MRI that it can do that scan, so that's an hour in an MRI. I've had a 20 minute MRI, I don't want to be in one for an hour. Then you can have a whole body low-dose CT, which that's not something that we frequently do in the United States, that's more of a European test. And then the next one's called a PET-CT scan. So that’s another… those are good ways that we can look in our bones and if we can see small lesions that those x-rays can't pick up, then we know we've got a problem and we should treat because it may cause you a problem sooner rather than later.

Cindy Chmielewski: Do you treat smoldering myeloma? Are there some smoldering myelomas that you treat? What's happening in the world of treatment in smoldering myeloma?

Are Patients Typically Treated for MGUS and Smoldering Myeloma?

Dr. Gregory: Oh, that's a really good question. So if you were in Spain, they would tell you that yes, you have to treat your smoldering myeloma. They've done a study. There was a physician named Dr. María-Victoria Mateos, and I'm kind of obsessed with her. She's amazing. And she does a lot of research. And her research has said that there's a survival benefit to treating smoldering myeloma. In the US, we don't take other people's word for it. We have to do the studies ourselves. And there are some of those studies that are ongoing, where we're following patients who are on a study to answer that question, “Should we treat?” And that data is becoming more and more mature. Right now, today, if I have a smoldering patient, I would not treat them unless it was on a study, but I have a feeling in the next couple of years that answer's probably going to change.