Expert Advice for Navigating Myeloma Treatment and Care Decisions from Patient Empowerment Network on Vimeo.
Myeloma experts Dr. Irene Ghobrial, Dr. Omar Nadeem, and Dr. Betsy O’Donnell, review essential testing that may impact the prognosis, care, and treatment options for patients with myeloma. The experts also discuss additional factors that are taken into consideration when choosing a therapy and share updates on new and developing myeloma research.
Dr. Irene Ghobrial is Director of the Clinical Investigator Research Program at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. Learn more about Dr. Ghobrial.
Dr. Omar Nadeem is the Clinical Director of the Myeloma Immune Effector Cell Therapy Program and Associate Director of the Multiple Myeloma Clinical Research Program at the Dana-Farber Cancer Institute. Learn more about Dr. Nadeem.
Dr. Betsy O’Donnell is Assistant Professor of Medicine at the Dana-Farber Cancer Institute specializing in Plasma Cell Disorders.
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Transcript:
Katherine Banwell: Hello and welcome. I’m Katherine Banwell, your host for today’s program. Today we’re going to hear perspectives from three myeloma experts on how to access personalized care for your myeloma. Before we get into the discussion, please remember that this program is not a substitute for seeking medical advice. Please refer to your healthcare team about what might be best for you.
Well, let’s meet today’s guests. I’ll start with Dr. Irene Ghobrial. Dr. Ghobrial, welcome. Would you please introduce yourself?
Dr. Irene Ghobrial:
Absolutely, and thank you for having us. My name is Irene Ghobrial. I am a professor of medicine at Dana-Farber Cancer Institute in Boston.
Katherine Banwell:
Thank you. Also with us today is Dr. Omar Nadeem. Thank you for being with us. Would you introduce yourself?
Dr. Omar Nadeem:
Hi, everyone. Thank you for having me. My name is Omar Nadeem. I’m an instructor in medicine at Harvard Medical School and I work with the faculty at Dana-Farber myeloma program.
Katherine Banwell:
Okay, lovely, thank you. And last but not least is Dr. Betsy O’Donnell. Thank you for joining us today. Would you introduce yourself to the audience?
Dr. Betsy O’Donnell:
Sure, and thank you for having us this morning. My name is Betsy O’Donnell. I’m an assistant professor of medicine at the Dana-Farber Cancer Institute specializing in plasma cell disorders.
Katherine Banwell:
All right. Thank you to all of you for taking the time out of your schedule to join us today. Before we delve into our discussion, let’s start with understanding the types of myeloma. Dr. Ghobrial, what is MGUS?
Dr. Irene Ghobrial:
So MGUS, or monoclonal gammopathy of undetermined significance, is a precursor or the stage before myeloma happens, and it’s actually a very common disease or entity in many, many of us as we get older. In fact, maybe 5 percent of the population over the age of 50 would have this early MGUS.
It doesn’t mean that it’s cancer. It’s a precursor to cancer, and we can talk more about it as we go on.
Katherine Banwell:
All right. Is it the same as smoldering myeloma, or is that something different?
Dr. Irene Ghobrial:
It’s not. It’s an earlier stage than smoldering myeloma, and it’s hard to actually make the right definitions. But currently what we say is if you have more than 10 percent cancer cells or plasma cells in your bone marrow, then it’s smoldering myeloma. And by the name, smoldering, it’s almost myeloma. It’s ready to go on fire, but it’s not there yet.
MGUS is before that, and the difference is that the chance of progression from MGUS to myeloma is only 1 percent per year, so many, many people will never progress to myeloma. While smoldering myeloma, just because there are more cancer cells in the bone marrow, has a higher chance of progressing, which is 10 percent per year. And in some people, a very high chance of progression of 50 percent in two years.
And we want to make sure that we catch those cases early and not wait for myeloma to happen.
Katherine Banwell:
How would you define myeloma?
Dr. Irene Ghobrial:
So, myeloma is currently defined as the same thing. The number of plasma cells in the bone marrow could be above 10 percent or more, or you have a protein in the blood. But the problem is that you’ve already had problems. You’ve had symptoms of end organ damage, so we have either high calcium, bone lesions, or bone fractures, anemia, kidney failure.
And then now or more recently, we added a few more things to tell us these people are going to really develop myeloma soon. So, it used to be part of smoldering myeloma, now it’s part of the definition of myeloma, so that we can treat patients earlier, which is if your light chain level is very high, above 100 for a ratio, or if you have multiple lesions by something called an MRI or a PET CT scan instead of the traditional X-rays, or if your bone marrow has a lot of the plasma cells, more than 60 percent.
And these were new definitions to make sure we don’t wait too much until people have an organ damage or symptoms and then we treat them. And you’ll hear from us that we think we should be treating people even earlier than that.
Katherine Banwell:
Well, thank you for that. That’s very helpful. Dr. O’Donnell, let’s move on to testing. What tests are necessary to help understand a patient’s specific disease?
Dr. Betsy O’Donnell:
Absolutely. So, testing really does depend a little bit on the stage at which your disease is found. In general, we use a very specific blood test that lets us know that there is clonal protein present. Remember, plasma cells are a type of white blood cell, and they make something called antibodies. We use a test called a serum protein electrophoresis, which is a blood test – an SPEP, we call it – that can tell us the difference between normal, healthy antibody and clone that are made from the plasma cells that we see in MGUS, smoldering, and multiple myeloma.
So, that’s a very important test, and sometimes your primary care doctor may notice that your total protein is elevated and send that test.
Or there may be other things that tip them off. Perhaps the kidneys are not where they used to be. And so that test is sent, and that’s the first tip-off that someone might have a plasma cell disorder.
Once we identify that there’s a plasma cell disorder, then that can set in place a workup, depending on the amount of clonal, monoclonal, M-protein that we see. So, sometimes that involves bone imaging. Historically that was a skeletal survey where we took lots of X-rays of your body. Now we have other tests we use. PET scans, CT scans, whole body MRIs. Sometimes it depends where you’re getting your treatment, and also it depends a little bit on your doctor’s degree of suspicion.
Bone marrow biopsies are a procedure that we sometimes do. We use a thin, hollow needle to take out just a little piece of bone, about the size of an inchworm, and take some fluid with it. There’s actually fluid inside the bone marrow.
And that can tell us, just as Dr. Ghobrial was defining the spectrum of plasma cell disorders, based on the percent of plasma cells, that can tell us where somebody belongs, which group they might belong in. So, we can use all of these tests to help give us a good sense of how much disease someone has and where in the spectrum or continuum a person is – MGUS, smoldering, or multiple myeloma.
Katherine Banwell: Okay, great. Thank you. I’m assuming these tests can help with understanding the stage of a patient’s myeloma. So, Dr. Nadeem, how is myeloma staged?
Dr. Omar Nadeem: Yes. So, myeloma is staged very differently than traditional cancers. Because this is a blood disease, we don’t really think about it like we may in other solid tumor cancers, where if it’s spread to multiple locations it’s four, etcetera. That doesn’t apply to multiple myeloma. It’s actually staged out of three stages, and uses your blood work for the most part, some blood tests, to help identify which stage you are. Historically, that has correlated with how you may do.
However, now we are learning that it’s far more to this story than just the bloodwork. So, we’re now using our bone marrow test results, particularly a test called a FISH test, which looks at the mutations that are present in examinable plasma cells, and if you have presence of some of these high-risk markers, that can actually either upstage you or downstage you if you don’t.
So, we’re now I think becoming a little bit smarter how we think about this disease. It’s not just based on some blood test. We’re actually looking at the biology of some of these cells and the amount in the bone marrow. A lot of times patients ask, well, if I have 50 percent, 60 percent, or 80 percent involvement of the bone marrow, that actually does not have anything to do with staging, right? So, I think it’s important to know that it’s actually a very unique staging system in multiple myeloma.
Katherine Banwell:
Okay. Dr. O’Donnell, the landscape of myeloma has changed significantly in recent years. How have advances in testing changed care from myeloma patients?
Dr. Betsy O’Donnell:
So, I mean, the landscape has changed incredibly just in terms of the treatments we have, and I think that Dr. Nadeem was talking about something really important.
In that when we look at FISH, which allows us to know the biology a little bit more, sometimes it helps us to decide kind of the risk that a patient is. We aren’t really at the point now where we do truly tailored therapies, like you see in some cancers, where we can detect specific mutations and pick drugs that align with that, but there are some that we do use. An example would be a drug called venetoclax (Venclexta), which works very well in patients who have a specific translocation, 11;14.
So, there is some degree in which we use that FISH and those cytogenetics to help define our treatments, but also really we’re just fortunate that we have new and evolving therapies. We’ve changed how we treat myeloma in the up-front setting, and then at the back end we have an exploding field of immunotherapies, CAR-T cells, bispecific antibody that we’re now using that really have tremendously benefited our patients.
Katherine Banwell:
Dr. O’Donnell, should all patients undergo in-depth testing, like cytogenetics?
Dr. Betsy O’Donnell:
Yes, so if you’re doing a bone marrow biopsy, absolutely. The question in terms of who needs bone marrow biopsies, if someone has a low risk MGUS, those patients don’t necessarily require a bone marrow biopsy. It’s an invasive procedure, it’s an uncomfortable procedure. But if we’re doing a workup for multiple myeloma or smoldering myeloma that includes a bone marrow biopsy, then absolutely.
Katherine Banwell:
Okay. Dr. Nadeem, what are you looking for with cytogenetics, and how might test results affect prognosis and treatment?
Dr. Omar Nadeem:
Yes, so as mentioned earlier, there are some mutations that are considered high risk, I will say with the caveat that we don’t fully understand every single mutation yet or have identified every single mutation yet that may be high risk or low risk.
But there are roughly five that we have identified that if a patient has one or two or several of those abnormalities, then their disease may behave a little bit more aggressively or may not respond as well to treatment.
However, I think myeloma is just very complicated, so we look at a lot of these results in the beginning, both whether they may be good or bad. But I think, ultimately, we have to see how patients do, and that by far is the most important prognostic factor, in my opinion. So, if we look at some of these tools, including staging, some of the bone marrow results and cytogenetics, and try to give some prediction in terms of what we may see from this person’s disease, but ultimately the treatments that are so effective now really dictate the course for the majority of the patients.
Katherine Banwell:
Are there specific tests that patients should ask for that could impact their care decisions?
Dr. Omar Nadeem:
Yes, I think it depends on where they are in their disease state. So, if we’re looking at whether a patient has a precursor or plasma cell disorder or multiple myeloma, then they need all the testing to help us figure that out.
So, that includes a bone marrow biopsy, the FISH testing as we just talked about. Advanced imaging like a PET scan or an MRI is now critical to identify patients that may have multiple myeloma versus those that have a precursor condition. So, we used to count on X-rays, as Dr. O’Donnell mentioned, but now really we do prefer one of those advanced imaging techniques for patients to undergo so that we can know.
So, I think if they have basically those tests completed, that gives us most of the information that we need.
Katherine Banwell:
Okay. Thank you for that. Let’s go back to asymptomatic myeloma for a moment. Dr. Ghobrial, how are people with MGUS monitored?
Dr. Irene Ghobrial:
Yes, so how do we even diagnose them, right? It’s a big question because it’s incidentally found. Someone will go to their primary care doctor and have a little bit of a high protein or slight anemia, and it may not be related, and then their doctor will check for serum protein electrophoresis, and that’s pure luck. We want to take away luck from this equation. We want to take away chance from this equation.
And we want to start screening people who are at risk, and we are doing that with the PROMISE study.
It’s online available to everyone nationwide, international now, where you can sign up on promisestudy.org and try to ask the question that we do for you research level, the serum protein electrophoresis, and a new test called mass spectrometry that is much more sensitive than SPEP to find it.
Now, once we find MGUS, we want to know what is my own personal risk of progressing to myeloma? Because I could be 30 years old with MGUS, and likely I will progress to myeloma in the next 10 years, 20 years, and by the time I’m age 60, I would have been diagnosed with myeloma. Just a true case in many, many people. If people are diagnosed today with myeloma, they are going to their doctor because they had back pain or anemia, and they are diagnosed with myeloma. In almost all of the cases, they would have had MGUS and smoldering, but they didn’t know about it three years ago, four years ago because they never got tested
for it.
Katherine Banwell:
Right.
Dr. Irene Ghobrial:
So, we want to change that completely and become proactive rather than being reactive and waiting for symptoms to happen. Once you have MGUS or smoldering, because we don’t know, we start looking for all of the things to help us identify your risk of progression. So, we look at the height of your M-spike. Is it small or big? And then we in many cases say okay, maybe you need a bone marrow biopsy if your M-spike is a little bit on the higher side because we don’t want to miss smoldering myeloma, which will change the prognosis.
And then we start looking at do you have anemia? Do you have kidney failure? Do you have any of the other things that may predict that you may be actually doing into myeloma?
