Early Signs of Multiple Myeloma: Symptoms, MGUS, and When to See a Doctor 

Beth Faiman:

This is Google search, right?

Dr. Joseph Mikhael:

Hi everybody. Dr. Joseph Mikhael here with the International Myeloma Foundation. And I am really privileged to share the stage today with a very dear friend I've known for many years, and you may know her, too. If you've joined us for our Facebook Live, if you've come to our in person or webinar events, you will have met the world-famous Beth Faiman. And it's my pleasure today to answer some of the most searched items related to the symptoms of multi myeloma.

And Beth, I'm going to hand you the board because you're the boss now.

Beth Faiman:

Thank you so much. What is multiple myeloma?

Dr. Joseph Mikhael:

Multiple myeloma is a cancer of the plasma cell. Plasma cells are cells that live in our bone marrow. That's why we think of myeloma as a blood cancer because the bone marrow is the factory of our blood. And these plasma cells are the ones responsible for making antibodies that fight off infections. Every time you get a vaccination, even every time you're exposed to things in the environment that your body thinks could be hazardous, you make antibodies against them. And these are good. It's important that we have antibodies. That's what keeps us alive.

But unfortunately, in myeloma, those same plasma cells that make good antibodies now become cancerous. And so they make, if you will, bad antibodies that have the opportunity and, unfortunately, the reality of attacking the body of damaging the kidney and the bones as we're going to discuss a little bit later. So, multiple myeloma then is a cancer of the plasma cell and it accounts for about 2% of all cancers.

It's not very common. It's more common in men than women, and it's twice as common in individuals like myself who are of African descent.

Any other thoughts about myeloma, Beth?

Beth Faiman:

People say, "So what do I tell my family?" And I just say it's making too much protein in your blood. It's not the protein that you eat that multiple myeloma is because I get that question all the time. Does it matter what I eat, how much protein I'm eating? It's just in the blood and it can attack your bone marrow. It can attack your kidneys. It can cause anemia. So, we have these crab criteria for who has myeloma. Some people have symptoms, but some don't, and we'll go over that as well. So, I think that might be on the next question, Dr. Joe. This is so hard to get off.

Dr. Joseph Mikhael:

What are the earliest signs and symptoms of multiple myeloma?

Beth Faiman:

And that is an excellent question because sometimes you have no signs of myeloma at all. We think of patients with multiple myeloma that tend to be in their fifth to seventh decades of life. Those are the most common age ranges. And you tend to have more back and bone pain, but who doesn't have back and bone pain when you're in your fifth to seventh decades of life, right?

So sometimes people let those symptoms go on and on before they seek care from a doctor or a healthcare provider about their symptom. But worsening back and bone pain consistently are the number one signs and symptoms. You might have anemia, which is a low hemoglobin level. Some people might feel tired or sluggish. Proteins in the blood can cause you to be tired because proteins are sticky. And then they pass through the urine. So some people might notice bubbles in their urine if their kidneys are involved.

So if you're noticing any signs or symptoms of something that doesn't seem right to you, talk to your healthcare provider and get some more information about your health. Anything else?

Dr. Joseph Mikhael:

No, you've said it really well. And in fact, I think you've got us going on the very next question, which is, when should you see your doctor? And I think that the point here that you made, Beth, is particularly important that we all get tired. We all at times get back pain, but it's when these symptoms really go beyond the usual fatigue, the usual pain.

The average patient sees their primary care provider three times with these kinds of signs and symptoms before myeloma is thought of, which is why the diagnosis is typically delayed six months in most patients, and even three to six months longer in African American and Latino American patients, often because they don't have as much access to primary care. So this question to me is really important that it's important to have this conversation with your doctor.

If you are experiencing pain that really seems out of keeping with the usual back pain that we all might feel once in a while, or have a fatigue that's more than, "All right, I didn't sleep well last night and I'm a little bit tired," but is really persistent and getting worse over time. Those are the kinds of things that really need to trigger an important conversation with your healthcare professional.

Beth Faiman:

And I would like to add, because I am a nurse practitioner and I've been so for 25 years, a lot of nurse practitioners, physician assistants are well suited to assess you for myeloma and diagnose you with myeloma monoclonal gammopathy. And we'll talk about the spectrum of plasma cell cancers as well, but it might not be a doctor. It might be a healthcare provider who is trained and able to obtain the test that you need to get to the accurate diagnosis.

So let's go to the next one. Okay. MGUS versus smoldering versus active myeloma. I can take this one, right?

Dr. Joseph Mikhael:

Please.

Beth Faiman:

Okay. So, Dr. Joe talked about this being a cancer of the bone marrow plasma cells. They're supposed to make proteins that protect you from getting sick. Unfortunately, they're dysfunctional proteins that don't work right. So there are different levels, right? So many people start with something called MGUS.

It's a little bit of extra protein in their blood or their urine, and they don't have any symptoms. And you should not have symptoms for MGUS. Maybe the protein is checked because you have neuropathy or something else along your body. But MGUS is the first level that many patients will live with and never need to be treated but monitored.

The second level is smoldering. And fortunately now, we have so much more evidence that people that are at high risk smoldering may actually need early treatment. So that's really important to be with the healthcare team that understands MGUS, myeloma, and smoldering as to whether or not that might be right for you.

And then the third level, of course, is multiple myeloma where you have that CRAB, hypercalcemia, too much calcium in your blood, renal or kidney problems, A, is anemia, and then bone damage. So we have the SLiM criteria, which Dr. Joe can comment on in a moment, but that is when people have to receive treatment urgently to stop the progression.

And then the goals of treatment are to get the protein as low as possible and stay as low as possible. And there's also the quality and quantity of life. And I can talk about this for hours. So I'm just going to stop there, and I'm going to see if you have anything else to add, Dr. Joe.

Dr. Joseph Mikhael:

I would just add that this is sort of an unusual situation where you have a cancer that's quite uncommon, myeloma, only 2% of all cancers, maybe about 36,000 to 37,000 new cases in the United States per year. Whereas MGUS, having that precursor condition, that little bit of protein you mentioned in the blood, that's extremely common. Five percent of people over the age of 40 have MGUS.

And we've learned over time that it's so important to watch those patients with MGUS because even though only a small proportion of them become myeloma, we want to detect them early. And that earlier detection is so important. That's really the focus of our whole discussion today is the earlier we can catch cancer, the better. And we're working, we're not there yet, but we're working ultimately towards screening programs where we may be testing people who don't have any symptoms whatsoever to see if we can detect it early like we do with breast cancer and we do with colon cancer.

Beth Faiman:

And the biggest question now is, do you screen everybody for MGUS? The answer is no, but there are some high risk populations that we are screening for cancer now with symptoms. So anyhow, let's go on to the next question and this is SLiMCRAB criteria. Explain.

Dr. Joseph Mikhael:

So because myeloma is sort of this unusual condition where a lot of people have the precursor, but few people develop myeloma, trying to define myeloma becomes really important because we don't want to tell people who have a tiny bit of protein in their blood that may never mean anything that they actually have a cancer that needs to be treated. So, for years, we used the CRAB criteria that Beth beautifully outlined.

Really quickly again, CRAB, high calcium in the blood, renal or kidney damage, anemia, or bone disease. About 12 years ago, we added three more criteria to that. I happen to give them the name SLiMCRAB so we could remember them. And it's four letters, but actually three things, S, L, I, and M. The S stands for 60, or 60% plasma cells in the bone marrow. Typically, in a normal bone marrow test, we should find less than 5% of our bone marrows are plasma cells.

By definition, myeloma, smoldering or active myeloma is over 10%, but even it can be over 10% and someone doesn't have any worrisome signs or symptoms that we don't treat them. But if it gets to 60 or higher, then we know that patient needs to be treated. The second part of SLiM is Li, referring to light chains. Those proteins that Beth described are composed of two beds, what's we call the heavy chain and the light chain. And sometimes those light chains can just circulate in the blood. They can grow high and they are the ones at risk of damaging the kidney. And so if we look at the ratio of what we call the Kappa or Lambda light chains, meaning the light chains that are involved with myeloma versus those that aren't involved, if that ratio gets over a hundred to one, then we know that person's getting very close to active myeloma and we need to treat them.

And the last one is the M. In SLiM, the MRI. If we do an MRI or imaging of the bone marrow and we see more than one, what we call focal area or area of activity in the bone marrow, that tells us that someone has active myeloma. So now we call it the SLiMCRAB criteria or myeloma defining events. If anybody has more than 10% plasma cells in their bone marrow, and any one of those seven that we think are related to myeloma, that's what we now define as active multiple myeloma.

Beth Faiman:

And that's why it's so important to seek an opinion at a specialty center. Somebody that does myeloma for a living. And I think that that's where the IMF is so wonderful at advocating. Think of how hard it is to make this a correct diagnosis. Do you need treatment or not?

So, if you're in the community and you're watching this, try to find and discuss with your healthcare team whether it's right for you to get a second opinion. That doesn't mean that that second opinion's going to take over and they're not going to take over your care and you'll never go back to your regular doctor, but getting an accurate diagnosis and knowing what type of myeloma you have is really important. That's all I'll say about that.

Before we go on to the next one, what are the signs and symptoms of myeloma relapse? Do you want to do this one or do you want me to?

Dr. Joseph Mikhael:

I'll start with this one. The reality is we've made huge progress in myeloma. People are going into remission, which doesn't mean cure, but it means the disease is controlled more quickly and for a longer period of time than ever before with the great new treatments we have in myeloma. But the sad reality is almost everyone with myeloma will have what we call a relapse or where the disease wakes up again.

And typically, we see it in the labs before we see it in the person as it were, which is why it's so important for patients to follow with their healthcare team because we look for that protein. Is it back? Is it back? Is it back? We'll usually see it start to climb slowly before any of that CRAB criteria manifests itself as well. Sadly, sometimes people can come back with kidney damage or with a bone fracture or something like that, but that's why it's so important to detect it carefully as the relapse starts to happen, Beth.

Beth Faiman:

And making sure that you know who is watching your myeloma. So I get to this all the time. I'm at an academic center and we partner with people in the community. And so we want to make sure to empower our patients to say, who's checking your myeloma labs? How often? And if there is a change, to have that discussion with the healthcare team, because that biochemical relapse where you're just having a rising of the protein that can occur, you might not have any symptoms of relapse.

Newer studies are suggesting we should maybe do more often imaging or bone marrow biopsies. And so that's to stay tuned. We don't know and do that for everybody yet, but talk to your healthcare provider and your healthcare team about the monitoring your myeloma is super important.

So the last one is when should family members be tested? Oh, we kind of talked about this in an earlier segment, Dr. Joe. What do you think about family members getting tested for myeloma?

Dr. Joseph Mikhael:

Yeah, it's a great question. I typically tell patients, almost all of our patients with myeloma, probably over 98% of them, we don't identify another family member with myeloma, but we know there are clusters of families that have more than one family member with myeloma. So if you have more than one first-degree relative that has multiple myeloma, it's worth a discussion with the family to say, should people be tested, in particular, if they're over the age of 40. But testing comes with challenges too, Beth, there's issues-

Beth Faiman:

And risks, yeah.

Dr. Joseph Mikhael:

... with insurance. There are issues with how frequently we need to do the testing. As the International Myeloma Working Group, we're working very hard to provide some concrete guidelines, but for now, it's a more a general discussion. We're not routinely testing all family members of patients with myeloma, but if there's two or more family members with myeloma, we may at least consider that testing.

Beth Faiman:

Yeah. And there are so many studies that are ongoing. I like the iSTOPMM study. It's a big study. They screened 79,000 or so, give or take, individuals over the age of 40. And as Dr. Joe mentioned, we know about 5% of the general population, especially in this study, has MGUS. So, do we want to put patients through repeated testing if it might not turn into anything worrisome?

So knowing the signs and symptoms, knowing your family history, and discussing with your healthcare team, and then you can decide what kind of screening might be right for you is what I would suggest. Are we at the end? Already?

Dr. Joseph Mikhael:

I think we're at the end.

Beth Faiman:

We're done!

Dr. Joseph Mikhael:

I think that's all we have time-

Beth Faiman:

All right.

Dr. Joseph Mikhael:

Now you get to pitch that, which is a good lead in to remind us that something very special is happening during March. March is Myeloma Action Month, and my BFF, Supna is going to hand me the next card to remind us a little bit about Myeloma Action Month. This is a month where we come together to raise awareness around multiple myeloma.

It is such an important thing for us to do. As we've just discussed, we want to be able to catch this disease earlier. When we catch it earlier, patients can get treated earlier, patients will live longer and better with this disease. So that's why we designate every year the month of March as Myeloma Action Month, and this year we're using a special hashtag.

Beth Faiman:

Yes, hashtag.

Dr. Joseph Mikhael:

You want to talk about the hashtag?

Beth Faiman:

Hashtag More Than Myeloma on social media. So social media, I think, is one of the best ways to get out there, get your voice heard. If you are a myeloma patient, a caregiver, care partner, if you have anybody that you know of that it's really important to you to share your story to get the word out, common signs and symptoms. And the more that you know about myeloma signs and symptoms, the more we can educate others.

What else would you say on this plaque is important?

Dr. Joseph Mikhael:

Well, I would say I love when people share their stories because that's the idea behind More Than Myeloma. You know Beth, I say it all the time. I don't treat myeloma. I treat people.

Beth Faiman:

Treat people, not myeloma.

Dr. Joseph Mikhael:

And we want to hear the stories of people who are living with myeloma and hopefully living well with multiple myeloma. We provide many resources for patients and for their care partners. You could join us at one of our live seminars, whether in person or online. We provide literally every month a different way that people can interact to learn about what is the newest, what is happening in multiple myeloma and how you can combat this disease.

Beth Faiman:

Events.Myeloma.org. And so you can sign up for newsletters. You can follow us on YouTube and that YouTube channel. It can be in person or online. And I send my newly diagnosed patients and their caregivers to that mMyeloma.org because of Milo, too, don't forget about how important Milo is, you can chat bot him in any language and he'll respond to you in your language, which I think is really important for patients too. And stay informed with the weekly newsletter. So that's important as well as the emails, right? How do you get an email?

Dr. Joseph Mikhael:

Absolutely. So, we prospectively send out every week information, we call the myeloma minute, to get updated what that's happening. And as you see here, if you go to subscribe.meieloma.org, you can sign up for that so that you can be really in the know of what is the latest that's happening.

And of course, we do have people who want to hear from you. We have an info line where our coordinators can walk you through this journey with you, that can help you and direct you to the resources that are going to be most helpful to you. And you can either call them directly at the number here, or you can email them at [email protected] (mailto:[email protected]).

Beth Faiman:

Especially if you have a sensitive question or something you don't want to be out there on the internet. Give them a call and discuss it with them. So I think with that being said, don't forget to hashtag MoreThanMyeloma.org. Subscribe to newsletters. Is there anything else I left out?

Dr. Joseph Mikhael:

No, I'm just really privileged to share the stage today with you, Beth. It has been a delight to do so because we want... Whether you've never heard of myeloma, whether you have myeloma, whether you're supporting someone through their myeloma. The IMF is here for you and we want to help you in every way possible.

Beth Faiman:

Yes.