Myeloma originates from a specific white blood cell found in the bone marrow called a plasma cell. Plasma cells play an important role in our immune system by producing different antibodies (also known as immunoglobulins) that help fight off infection.
In myeloma damage occurs to the DNA of developing plasma cells causing them to transform into cancerous myeloma cells. These damaged cancerous cells start to multiply and spread, crowding out our bone marrow so it can’t make enough normal healthy blood cells.
Instead of making helpful immunoglobulins that fight off infections these myeloma cells only make one type of abnormal immunoglobulin called a monoclonal or paraprotein. This Paraprotein has no useful function in the body and can build up in your blood and urine where it can cause some of the symptoms of myeloma.
How does myeloma develop?
All people who develop myeloma initially had a pre-cursor condition called Monoclonal Gammopathy of Undermined Significance (MGUS). People with MGUS produce a low level of paraprotein in their blood or urine that does not cause any symptoms or damage to the body and does not require treatment. Most people live with MGUS without knowing they have it. People with MGUS will be monitored with blood tests to check the paraprotein level over time. While everyone with myeloma once had MGUS it’s important to know that not everyone with MGUS will go on to develop myeloma.
Some people discover that they have a paraprotein in their blood or urine and abnormal plasma cells in their bone marrow but still otherwise feel well and have no symptoms. This is called Smouldering Myeloma and like MGUS doesn’t require treatment. If you have smouldering myeloma you are more likely to develop myeloma so closer monitoring with more regular blood tests to check the paraprotein level is required.
What causes myeloma?
Although there has been a large amount of research into myelomas potential triggers, no definite causes have been confirmed.
Some risk factors that could increase your chances of developing myeloma include your age (myeloma is more common in people aged 60 years and over) and a lifetime of accumulated exposure to certain chemicals, radiation, viruses and a weakened immune system.
Myeloma is not thought to be hereditary (passed down genetically in families). However, you are more likely to develop myeloma if you have a family member who has been diagnosed, although this is very rare. There are no screening tests for myeloma and no way of predicting who will develop a paraprotein.
Types of myeloma
Myeloma is often described as being a very individual disease with symptoms experienced and response to treatment varying greatly. Some of these differences are because of the different biological types of myeloma.
One of the ways of classifying myeloma is based on the type of abnormal immunoglobulin, or paraprotein, that the myeloma cells produce. Each immunoglobulin (called Ig for short) is a Y-shaped structure that is made up of two heavy chains and two light chains.
There are five possible types of heavy chains, and these are labelled using the letters G, A, D, E and M. There are two possible types of light chains, and these are labelled using the Greek letters kappa (ƙ) and lambda (ƛ).
Each individual immunoglobulin can have only one of the five possible heavy chains and only one of the two possible light chains. These combinations are what define the different Ig types of myeloma:
- IgG kappa or lambda (most common type, makes up 65% of myelomas)
- IgA kappa or lambda (second most common type)
- IgM kappa or lambda (rare)
- IgG kappa or lambda (rare)
- IgD kappa or lambda (rare)
About 20% of people with myeloma produce light chains only (kappa or lambda). This is called light chain or Bence Jones myeloma. This is the type of myeloma that’s most likely to cause kidney damage, as excess light chains are removed from the body through the kidneys.
In about 1–2% of cases, myeloma cells produce very little or no immunoglobulin of any type. This is called non-secretory myeloma, making diagnosis and monitoring more difficult.
Is myeloma curable?
Myeloma is often considered as a chronic or ongoing condition that people live with over the longer term. After initial treatment, it will return, when it does it will need different types of treatment to help get it under control until it returns again. This is sometimes called a relapsing-remitting cancer and makes it different from many other cancers.
While myeloma currently cannot be cured, there are many treatments that are able to slow its progress, put it into remission or plateau phase, control symptoms, and give you the best quality of life for as long as possible.
With many new developments in its treatment and management, the outlook for myeloma is improving all the time. Research is continuing to develop new treatments and find ways to use existing treatments more effectively. These advances are having a very positive impact on survival rates, and people with myeloma are now living longer than ever before.
Basic facts
What are the symptoms of myeloma?
Signs and symptoms of myeloma may be vague and like those of other conditions, which is why it can take quite some time for myeloma to be diagnosed for many people.
The most significant myeloma symptoms are often described using the acronym CRAB where each letter stands for different symptoms:
C- Calcium elevation (increased calcium in your blood, also called hypercalcemia)
R- Renal insufficiency (reduced functioning of your kidneys)
A- Anaemia (low red blood cells)
B- Bone involvement (bone pain, fractures, bone weakening and tumours called lytic lesions)
Some other symptoms of myeloma include:
Fatigue (extreme tiredness that doesn’t improve with rest or sleep)
Recurrent infections (having lots of infections or infections that take a longer than usual to recover from)
Peripheral neuropathy (damage to nerves causing changes in sensation such as burning, tingling and numbness. Most commonly in the hands and feet)
Hyper viscosity (thickening of the blood caused by the myeloma cells leading to headaches, blurred vision and high blood pressure)
What tests are used to diagnose myeloma?
Diagnosing and monitoring myeloma is like putting together pieces of a jigsaw puzzle. Many different tests and other investigations are used to build the picture for each person. As myeloma is a very individual condition, the types of tests used may vary from person to person.
Some of the common tests your doctor may order include:
Blood tests:
- Serum protein electrophoresis or SPEP (measures your paraprotein and free light chains)
- Full blood count (measures the makeup of important cells in your blood including red blood cells, white blood cells and platelets)
- Urea and creatinine (measures how well your kidneys are working)
- Calcium (myeloma can cause high levels of calcium in the blood)
- Beta 2 Micro globulin or B2M (a molecule that in high levels can indicate active myeloma)
- Albumin (a type of protein that can decrease with active myeloma)
- Lactate dehydrogenase (an enzyme that at high levels can be a sign myeloma is active)
Urine tests:
A urine test may be used to check for myeloma cells, which are called Bence Jones protein when found in urine.
Your urine might be collected as a small sample or a 24-hour urine collection, which involves collecting your urine at home over a 24-hour period.
Imaging (scans):
Myeloma can affect your bones, and so it’s important to keep an eye on your bone health, which can be done using a range of different types of imaging or scans.
- Whole-body low-dose CT or WBLDCT (CT scans and can identify myeloma-related bone changes and bone damage called lytic lesions)
- Magnetic resonance imaging or MRI (shows the amount and pattern of myeloma in your bone and bone marrow, and sometimes outside the bone)
- Positron emission tomography-computed tomography or PET/CT: (involves having a radioactive medicine called fluoro-deoxy-glucose injected into a vein to highlight areas of rapid cell growth such as tumours)
Bone marrow biopsy:
A bone marrow biopsy or BMAT is a procedure that looks for the percentage of plasma cells in your bone marrow. The procedure is done under a local anaesthetic with pain relief. A thin needle is used to take a small sample of fluid (aspirate) and a small core of bone (trephine) from your bone marrow – usually from your pelvic bone. These samples are then examined under a microscope. Normal bone marrow has fewer than 5% plasma cells; bone marrow in people with myeloma may have between 10% and 90% plasma cells.
Cytogenetic testing:
Cytogenetic testing involves testing samples of bone marrow to look for changes (mutations) in chromosomes, which are the structures that carry genetic information in our cells. This is usually done using a test called fluorescence in situ hybridisation (FISH). This information may be used to guide treatment choices.
How is myeloma monitored?
You will have regular blood tests where your paraprotein and light chain levels are measured. Your paraprotein results show how your myeloma is responding to treatment, if you need to start treatment or if your myeloma remains stable or in remission. Your treating team will let you know how often you will need to have these tested as it can be different for each person.
The treatment and management of myeloma is very individual, just like the condition itself.
When you do begin treatment, it will usually be made up of a combination of two or three different medicines, called a treatment regimen. This helps to ensure that the myeloma cells are being targeted at different points of their life cycle to achieve the maximum response. The aim of treatment is to achieve maximum response without unacceptable side effects.
Your doctor will explain the treatment options available to you at diagnosis and at each relapse.
There are many factors that you and your doctor will consider when making treatment decisions, these include:
- Availability of the treatment through the PBS, a clinical trial, or special access program
- Your current level of myeloma
- Your general health and age
- Any pre-existing health conditions you have
- Your response to any previous treatments
- Side effects you experienced with previous treatments
- Your personal preference due to circumstances and lifestyle
Types of treatment
Types of treatment used to treat myeloma include:
- Chemotherapy or chemo
- Stem cell transplant or SCT
- Steroids
- Immunomodulators or ImiDs
- Proteasome inhibitors or PIs
- Monoclonal antibodies or mAbs
- Selective inhibitors of nuclear exports or SINEs
- Chimeric antigen receptor T-cell therapy or CAR T-cell therapy
- Antibody-drug conjugates or ADCs
- Bi-specific T-cell engagers
- BCL-2 inhibitors
What is maintenance treatment?
Maintenance treatment is treatment that aims to maintain or further deepen your response to a line of therapy. This might involve:
- Continuing with a current treatment regimen at a lower dose or with less frequent doses
- Starting a lower-dose treatment following stem cell transplant
Not all people being treated for myeloma will need maintenance treatment.
Side effects of treatment
All medicines, including treatments for myeloma, have side effects that you need to be aware of. The type and severity of side effects is different for each person, so it’s important to let your treating team know about any changes you are experiencing, even if you’re not sure that they have been caused by a treatment. In most cases, there are simple tools and tips that your team can recommend to help you feel and function better.
The most common side effects of myeloma treatments include:
- Fatigue
- increased risk of infections
- anaemia (low red blood cells)
- nausea
- appetite changes
- diarrhoea
- constipation
- changes to sensations in your hands and feet (peripheral neuropathy),
- blood clots
- mood changes
- sleep disturbances
- problems with short-term memory and concentration (‘chemo brain’)
Talk to your treating team about side effects that are specific to the treatment you are receiving.
How will I know treatment is working?
Once you have started treatment, you might notice some of the symptoms caused by myeloma start to reduce. This can be a sign that treatment is working. Your doctor will monitor your response to treatment regularly, usually through blood and/or urine tests. They might also order scans or a bone marrow biopsy to check for a reduction in your bone lesions or plasma cells in your bone marrow.
Getting a second opinion
There may be times when you or your doctor feel that you would benefit from the opinion of another haematologist (myeloma specialist).
Because myeloma accounts for less than 2% of cancers overall, and choosing the right treatment is sometimes complex, you may need a second opinion to ensure that your diagnosis is correct, the treatment plan is appropriate, and that all other options have been considered.
What if I don’t want treatment at all?
You may decide that you don’t want to have any treatment. In this case, it’s important to have an open conversation with your treating team about your wishes. They will then recommend supportive measures that can help to relieve any symptoms. The priority for your care will simply change from treating the myeloma to keeping you functioning as well and as comfortably as possible.
What are clinical trials?
Treatments and outcomes for people living with myeloma are constantly improving, and the main way this happens is through clinical trials, where new treatments can be developed, evaluated and compared with current treatments.
Clinical trials provide a robust and ethical way to find out if new treatments are safe and effective, and the results of these trials help to decide which treatments will be reimbursed through the Australian Pharmaceutical Benefits Scheme (PBS).
Participating in a clinical trial can provide the individual person with myeloma with a better outcome, and can also benefit other people with myeloma who may eventually receive the treatment being trialled.
Accessing clinical trials
Each trial is designed to focus on treating different stages of myeloma, and each will have its own inclusion and exclusion criteria that need to be met for someone to be included in the study.
To learn more about clinical trials currently available in Australia, talk to your treating team and ask if there is a clinical trial that might be suitable for you.
You can also search for clinical trials on www.australiancancertrials.gov.au or www.clintrialrefer.org.au