Transcript
[0:00 – 1:10] Introduction
Emma Huybens: Um, I’ll now introduce our first speaker who will be presenting on a myeloma overview, a topic that is new to some and a wonderful refresher before diving in deeper for others. Dr. Angie Young completed her hematology training in South Australia and a clinical myeloma fellowship at the Royal Adelaide Hospital. She’s working as a consultant hematologist at the Royal Adelaide Hospital and Lyell McEwin Hospital. Her areas of interest involve plasma cell disorders, including myeloma and amyloidosis. Welcome Angie.
Dr. Angie Yong: Hello. Good morning everyone. Thank you for this opportunity to… I’d like to say give a speech but I think you know let’s put it this way. Let’s have a chat about what myeloma is. We’ve got a brief overview. We’ve got a few other speakers who will be covering treatment and investigation. So I haven’t really touched much on that. Let’s go back to basics.
[1:11 – 4:31] What is Myeloma & Statistics
So the first question is, what is myeloma? Myeloma is a cancer. It’s a cancer involving the bone marrow. In my next slide you will see what the role of the bone marrow is. However, what happens in myeloma is that there is a certain type of white cell which becomes a plasma cell, which is part of the immune system of the body, and in myeloma there is an abnormal production and some of these plasma cells which are abnormal are also increased in numbers. These abnormal cells can then deposit in organs such as the kidneys or the bones and they cause quite classic myeloma symptoms. Of course, not everyone presents the same way.
So, this is a slide, the most recent one that I could find on the statistics of myeloma in Australia. This is from 2021. For 2021 there has been an estimated 2,423 people diagnosed with myeloma. Slightly more males than females. Of all the cases of cancer that were diagnosed in 2021, myeloma accounted for 1.6%. In the number of deaths from myeloma in 2021 there were a total of 1,074. To put it into perspective, in terms of mortality from all sorts of cancer, the deaths from myeloma accounted for 2.2%.
So in a way when we look at the statistics, myeloma is actually not that common a cancer, but it can be quite debilitating. Now the chances… it says that in general people have a 54% chance of surviving for at least 5 years with myeloma. But bear in mind that this particular number was from 2013 to 2017 and there’s been many, many changes in the treatment of myeloma since then. I expect, and I’m hoping, that the number will be higher when we have our next round of statistics.
So, unfortunately the pictures are not that clear, but what I have here on the left in the diagram is the numbers of different types of cancers diagnosed in Australia, and you can see that myeloma, which is highlighted in brown, is not the most common. On the right, the diagram shows the rate of diagnosis of myeloma from 2017 to 2021. And you can see that the numbers of people diagnosed with myeloma has been slowly increasing.
[4:32 – 6:26] Bone Marrow Basics
Yes. So, what exactly is myeloma? What is a bone marrow? We have bones. This is our skeleton. The bones are hard, and if you look at the middle diagram there is a compact bone, the cortex, which is the hard calcified part. But inside there is the spongy part, and this is the bone marrow. The bone marrow makes our blood cells. It makes red cells, white cells which are the overall immune system of the body, and it makes platelets. I call platelets the tiny frontline ‘guts’ of your immune system. The platelets are the ones that, if you cut yourself, get activated first to try and activate all the proteins in your body to start healing that cut.
Now, white cells: there are different types. We have lymphocytes (B-lymphocytes, T-lymphocytes). These are key to the immune system. We have monocytes, which are reactive white cells that try to defend the body against infection. Together with neutrophils, they try to ‘eat up’ bacteria and invaders. The other two are eosinophils, which are elevated during allergic reactions, and basophils. Each of these different types of white cells play a different role. With myeloma, what we are focused on is the lymphocyte lineage.
[6:27 – 9:53] How Myeloma Develops
So what happens in myeloma? A healthy bone marrow on the left would produce lymphocytes. B-lymphocytes are what we are interested in. Some of these lymphocytes would then differentiate into plasma cells. The plasma cells secrete antibodies, and these are the normal antibodies of the system. So, in very basic terms, if you’ve had a vaccination, your immune system recognizes that vaccine and the plasma cells are the ones that remember the antigen (with this little ‘Y’ looking thing). They remember the exposure and can be primed to activate the immune system if you encounter the same infection again.
In myeloma, this process goes a bit haywire. The bone marrow makes B-lymphocytes, but unfortunately something triggers it to just make a particular type of plasma cell. So it’s not an all-round general secretion of antibodies. It triggers one type of plasma cell to be produced in excess. Therefore, that particular plasma cell type will be in large numbers and will only be secreting one type of antigen. Because it’s only one type, we call it a monoclonal protein. You may have heard that term from your doctors. So that’s what it means. On the right is a diagram of what a monoclonal protein looks like.
So in myeloma, sometimes the plasma cells secrete this whole structure. We call that the monoclonal protein. Some people have IgG myeloma, some have IgA myeloma. That just refers to the type of heavy chain (in light green on the diagram). This helps identify the type of monoclonal protein.
In some cases of myeloma, it’s not the entire structure that is secreted. These abnormal plasma cells make too many light chains. Light chains are part of the structure (the dark blue aspects). So the little side chains here consist of kappa and lambda light chains. Some people’s myeloma only secretes this particular bit. It can be kappa or lambda. For these myeloma classifications, we call them light chain myeloma. So it’s still a similar process of abnormal production, but what the plasma cells are secreting is what gives the myeloma its name: IgG myeloma, IgA myeloma, or kappa/lambda light chain myeloma.
[9:54 – 10:34] Types of Myeloma
Does an IgG myeloma behave differently from a light chain myeloma? Sometimes it does. Light chains can cause quite a lot of kidney problems if they are too high. This is something that would be determined on a kidney biopsy. But in general, whether it’s the whole antigen, an IgG/IgA myeloma, or a light chain myeloma, we look for similar symptoms.
[10:35 – 14:16] The “CRAB” Symptoms
So the common symptoms of myeloma, an easy acronym to remember, is CRAB.
C: Myeloma can cause increased calcium in the blood. In quite severe cases, this can be associated with abnormal, almost life-threatening palpitations. It can cause confusion if the calcium levels are too high.
R: Some myelomas present with kidney problems. The myeloma protein or light chains deposit into the kidneys and affect their function. The kidneys filter the blood and remove toxins, and this process is impaired. So people with kidney problems may be very lethargic, find they are going to the toilet often, or that their legs are quite swollen. I have had patients tell me they’ve gone up two or three shoe sizes from the swelling.
A: A stands for anemia. So a drop in red cell count leads to fatigue, lethargy, and general muscle weakness.
B: Bone pain. This is one of the more common warning signs. So some people who have unexplained bone pain, back ache, or scans showing lytic lesions. Lytic lesions are described as little ‘punched out’ lesions. If you look at a plain X-ray film, you can sometimes see little holes, and that’s quite abnormal. The other bone involvement is crush fractures. When there’s myeloma in the bones, they get quite frail, and stress can result in vertebrae becoming compressed. Sometimes in myeloma, plasma cells can grow out of the bone and cause a lump, or plasmacytoma.
Other non-CRAB features include weight loss, fevers, and hyperviscosity syndrome. Some people with a very high protein level can have blurry vision or headaches because the thick blood affects vision. That’s something we have to be careful about.
[14:17 – 19:36] Key Investigations
So what investigations do we do for myeloma? The first investigation is a blood test. We look for anemia, high calcium, and check kidney function. In addition, some blood is sent to the lab to look for the amount of monoclonal protein. That’s called serum protein electrophoresis. That test takes a few days to run. We also check circulating kappa and lambda light chains in the blood. All this helps us screen for myeloma.
Another test is a urine test. Light chains circulate. If there’s a lot, they can go into the kidneys and be secreted in urine. These light chains in urine are called Bence Jones protein. I like to ask for a 24-hour urine collection. Sometimes secretion can be intermittent, so over 24 hours I like to know how much Bence Jones protein is being secreted. It also helps me know about kidney function. On a side note, if someone is losing a lot of protein, it could hint at a coexisting condition like amyloidosis.
The third thing we do is a scan. Recent guidelines recommend a skeletal survey, which is imaging of the main bones: the spine, skull, long bones, ribs, etc. The recommendation is for low-dose CT scan because it’s more sensitive. However, a CT skeletal survey is often not Medicare reimbursed, so an X-ray skeletal survey may be used. An X-ray is good, but CT is more sensitive. We’ll do what’s necessary. Other tests include MRI scans for ongoing back pain, and PET scans. A PET scan looks at metabolic activity (glucose metabolism) to see which spots have active disease. A PET scan for myeloma is also not Medicare rebatable, so access is limited.
[19:37 – 24:51] The Bone Marrow Biopsy Explained
The final test is a bone marrow biopsy. Some patients ask, if I already have a blood test showing high monoclonal protein, why do I need a bone marrow biopsy? I explain that from the bone marrow samples, I can send for tests I can’t get from blood.
What exactly is a bone marrow biopsy? Different centers do it differently, but typically it’s done at the back of the pelvis (the posterior superior iliac spine). The patient lies on their side, pulls their knees up, and a needle goes into the spongy bone marrow. It’s usually a straightforward procedure under local anesthetic. Most patients feel a bit of ache but are fine the next day.
What do we look at? First, we take an aspirate. When the needle is in, a little bit of liquid bone marrow (which looks like blood) is taken out and smeared on a slide. We look at it under a microscope. It tells us about the white cells, red cells, and whether there are abnormal numbers of plasma cells. We can see what the plasma cells look like.
Second, we take a trephine or core biopsy. The needle is gently rotated to take a small core of bone marrow. This is processed, sliced thinly, and put on a slide. This lets us look at the architecture of the bone marrow. Is it orderly? Is myeloma overtaking the normal marrow? Some places also do clot sections, another way of seeing the architecture.
What samples from the bone marrow are different from blood? We send the aspirate for immunophenotyping (looking at lymphocyte surface markers). This helps us see what kind of markers the abnormal plasma cells express. Interestingly, sometimes we find a coexisting lymphoma this way. The last and most important test is genetic testing. We look at the karyotype (chromosomes) and FISH (Fluorescent In Situ Hybridization) for genetic mutations in the abnormal plasma cells. Some mutations make myeloma more aggressive. This is important for diagnosis and prognosis. We cannot do these genetic tests on blood; we need the bone marrow sample.
[24:52 – 26:00] Genetics & Staging (R-ISS)
We use the Revised International Staging System (R-ISS) to stage myeloma. This is based on certain criteria: we look at albumin and LDH (lactate dehydrogenase, a marker of cell turnover) in the blood, and beta-2 microglobulin (a protein on B-cells and plasma cells; if high, it generally means a high burden of disease, but it’s also affected by kidney function). Then we add in the genetic mutations from the bone marrow. Some mutations are higher risk.
Why do we stage? Whether we are stage 1, 2, or 3 does not usually change the initial treatment we give, as treatment is based on PBS availability. But it helps with prognosis. Knowing the stage might influence decisions, like considering two stem cell transplants instead of one for a young person with high-risk disease. I like to have as much information as possible.
[26:01 – 30:23] MGUS vs. Smouldering vs. Active Myeloma
We have normal B-cell production at the top. That’s normal bone marrow. Lymphocytes become normal plasma cells secreting a full range of antibodies. In myeloma, we have abnormal plasma cells secreting a monoclonal antibody, causing organ damage (the CRAB features).
Some people are in an in-between phase called MGUS (Monoclonal Gammopathy of Undetermined Significance). There are some plasma cells secreting a monoclonal protein, but not at a high level or number. It’s like a precancerous condition. There are no CRAB features. For people with MGUS, there is an increased risk of fractures and it can be common in the elderly (5-8% of people over 75). For MGUS, our GPs should monitor the monoclonal protein once or twice a year.
You may have heard of solitary plasmacytoma. That’s when abnormal plasma cells are found in one spot (like a spine or rib) causing a lump, but there is no evidence of myeloma elsewhere in the bone marrow and no CRAB features. Usually, radiotherapy is the main treatment.
Smouldering myeloma is when people have a moderate number of abnormal plasma cells or monoclonal protein, but still no CRAB features. It’s called ‘smouldering’ because they may develop myeloma soon.
Non-secretory myeloma: patients have abnormal plasma cells causing typical myeloma features (bone lesions, etc.), but those cells do not secrete a monoclonal protein or light chains into the blood or urine. Diagnosis is from the bone marrow biopsy.
Plasma cell leukemia is when there are circulating abnormal plasma cells in the blood. It’s a sign of aggressive, often end-stage disease.
[30:24 – 35:06] Other Conditions & Risk Factors
There are other conditions related to plasma cells but which are different from myeloma.
POEMS syndrome is a different disease where there is a monoclonal protein, but it manifests with neuropathy, organ enlargement, endocrine problems, and skin changes.
AL Amyloidosis is an abnormal, misfolded protein. In some cases, the amyloid is driven by the abnormal plasma cells of myeloma. It’s said that 10% of myeloma patients can have amyloidosis as well, though it can be hard to find.
Lymphoplasmacytic lymphoma has abnormal cells somewhere between a B-cell and a plasma cell, causing more of a lymphoma than a myeloma.
Can myeloma be inherited? Myeloma is not considered a hereditary disease. But the risk of developing myeloma does increase if you have first-degree relatives (parents, siblings) with myeloma. Other risk factors include: prior MGUS, prior solitary plasmacytoma, being of African descent, and prior exposure to radiation or benzene (though this also increases risk for other cancers).
[35:07 – 38:49] When to Start Treatment
Just quickly, treatment for newly diagnosed symptomatic myeloma: anyone who is symptomatic with CRAB features should start treatment. We aim for control so organs don’t deteriorate.
What about smouldering myeloma? If you have a high number of plasma cells but no CRAB features, why aren’t we treating? If there are no CRAB features, the mainstay is still monitoring. However, there are criteria called “biomarkers of malignancy”: if bone marrow plasma cells are >60%, if the abnormal/normal light chain ratio is above 100, or if an MRI finds more than one focal lesion. If someone meets these criteria, they should be considered for treatment as if they have symptomatic myeloma.
For solitary plasmacytoma, radiation is the main treatment. For MGUS, monitoring is the mainstay; there’s no evidence treating it earlier makes a difference. A good GP can monitor with blood tests.
For smouldering myeloma without the high-risk biomarkers, monitoring remains key. There is a Mayo Clinic “20-2-20” criteria identifying high-risk smouldering myeloma, and some hematologists consider treatment then, but it’s not a widely standardized approach. The other option for smouldering myeloma is enrolling in a clinical trial, as we are still learning.
[38:50 – 43:04] Treatment Approaches & Goals
In general, treatment for newly diagnosed myeloma is: a short course of induction therapy, then if appropriate, an autologous stem cell transplant, followed by maintenance therapy. For older or frail patients, stem cell transplant may not be the best option, so induction therapy plus/minus maintenance is considered. Radiotherapy or surgery may be needed for bone issues (e.g., an impending hip fracture). All this, and clinical trials, should be discussed with your treating hematologist. Treatment is targeted to your myeloma, age, and other health conditions.
A common question: can myeloma be cured? Unfortunately, myeloma is not a curable cancer yet. A lot of progress has been made in the last 10+ years, so watch this space. Our main aims are to control the disease and achieve remission.
As of May this year, there are new PBS-funded treatments for newly diagnosed myeloma. The common combinations will be tailored to you. Treatment is always individualized.
Stem cell transplant fitness needs to be assessed. For relapsed myeloma, there are many PBS-funded options and clinical trials, including CAR T-cell therapy, antibodies, and more. The future and overall survival for people with myeloma is looking very promising.
[43:05 – 47:55] Supportive Care Essentials
Supportive care is very important. We need to aim for good quality of life.
- Pain & Bones: Bone pain relief is essential. Radiotherapy can give quick pain relief at a specific site. Surgery may be needed for bones at risk of fracture.
- Bone Protection: Even without bone lesions, there is increased bone destruction. Bisphosphonates (like zoledronic acid) are important to slow down bone turnover and destruction. This should be considered for everyone with myeloma. Crucially, before starting bisphosphonates, ensure you have a good dental review. There is a rare but serious condition called osteonecrosis of the jaw, and good dental health is the main prevention.
- Infection Risk: Having myeloma itself suppresses normal antibody production. Be careful, keep up with vaccinations (discuss with your hematologist), and be vigilant.
- Treatment Side Effects: Manage risks like high sugars from steroids, gastritis (use stomach protection), and increased clotting risk from both myeloma and some medications.
[47:56 – End] Resources & Q&A
A few helpful local resources: Myeloma Australia, the Leukaemia Foundation, and the Cancer Council website.
[Q&A]
Emma: Thank you so much Angie. We have a couple of questions. The first one from Janine: “How high can your paraprotein levels go before it causes damage?”
Dr. Yong: It doesn’t need to go high before it causes damage. Remember the slide about plasma cells. Sometimes you can have a low paraprotein of 8 or 10 and have a lot of bone or kidney features. In non-secretory myeloma, there’s no paraprotein at all, yet people get full CRAB features. So the number doesn’t tell you you’re safe. It’s more related to the scans and what’s happening. It’s not one-size-fits-all, which makes myeloma tricky to explain.
Emma: We have time for one last question. “I have smouldering myeloma. Is there anything I can do to prevent it from transforming into multiple myeloma?”
Dr. Yong: I get that question a fair bit. The short answer is no. There is unfortunately not much to do to prevent transformation. But what I always say can be done is: keep healthy, keep fit. Make sure your dental review is fine. So when the time comes for treatment—and we don’t know when that will be—you are as prepared and as fit as possible to have the best outcome.
Emma: Thank you so much again Angie for your time today.
