What is myeloma?

Myeloma is a blood cancer that starts in the plasma cells of the bone marrow. Plasma cells are blood cells that make proteins called immunoglobulins. They help fight infection. In Myeloma, myeloma plasma cells accumulate in the bone marrow. They leave no room for the bone marrow to make healthy blood cells. People with myeloma are often tired due to a low red blood cell count. They may get recurrent infections due to faulty plasma cells.

Myeloma plasma cells make an abnormal immunoglobulin called paraprotein, M-Protein, M-spike or myeloma protein. These have no useful function. Paraproteins are found in the blood and/or the urine in most patients. Non-secretory myeloma is only found and monitored by scans and bone marrow biopsies. Paraproteins can build up in the kidneys and other organs, causing damage. The type of myeloma you have is named after the paraprotein it produces.

Myeloma cells also produce a chemical that stimulates cells called osteoclasts. Osteoclasts break down bone tissue. The tissue breaks down bone faster than it can be rebuilt. This weakens bones and causes problems including:

• Bone fractures – from increased osteoclast activity.
• Bone pain – due to the weakened bones, especially the spine. This can put pressure on nerves.
• Bone lesions – are small holes or lesions in the bone. This makes the bones weaker. They are also called lytic lesions.
• Hypercalcaemia – happens when bones break down and calcium is released into the bloodstream. It can cause symptoms of confusion, nausea, constipation and weakness.

Causes of myeloma

There is no specific cause for myeloma. It is more common in men than women. The risk of developing myeloma increases with age. Some factors that can increase your risk of developing myeloma include:

• A history of monoclonal gammopathy of undetermined significance (MGUS).
• Family history of myeloma.
• Some viruses and autoimmune diseases.
• Radiation exposure – previous radiation therapy or high level environmental radiation exposure.
• Hazardous chemicals – exposure to high levels of environmental chemicals.

Understanding immunoglobulins

Immunoglobulins (Ig), also called antibodies, are made by our plasma cells. These are made in the bone marrow. Antibodies protect us from and help fight infection. In myeloma, lots of abnormal plasma cells are produced. These cells make abnormal immunoglobulins called paraproteins.

Each protein is made up of:

• Heavy chains – 2 long protein chains
• Light chains – 2 shorter protein chains

Some types of myeloma, like light chain or Bence Jones myeloma, only produce the light chain part of the paraprotein. These are called free light chains.

There are different types of heavy and light chains:

• Five types of heavy chains – G, A, D, E and M
• Two types of light chains – kappa and lambda

IgG kappa myeloma:

• Is the most common myeloma. IgG is the most common immunoglobulin in our immune systems.
• It produces immunoglobulins that have heavy chains bound to light chains.
• It has two IgG heavy chains bound to two kappa light chains.

Stages of myeloma

To work out your stage, your haematologist will look at some blood test results:

• Beta-2 microglobulin – protein on myeloma cells
• Albumin – protein in the blood,
• Lactate dehydrogenase (LDH) – indicates blood cell damage
• Fluorescent in-situ hybridisation (FISH) – cytogenetic test to look at chromosomes

Comparison of blood test results with Myeloma disease stage.

R-ISS stage	Beta-2 microglobulin level (mg/L)	Albumin level (g/dL)	Lactate dehydrogenase (LDH) level	Chromosomes
Stage 1 Low risk	Less than 3.5	Greater than or equal to 3.5	Normal	No high-risk chromosomes
Stage 2 Low-intermediate risk	Not stage 1 or 3
Stage 3 High risk	More than 5.5		High	High risk chromosomes

Symptoms of myeloma

The symptoms of myeloma depend on how advanced the disease is. In the earliest stages, there may be no symptoms, and myeloma is picked up during a routine blood test. In the more advanced stages of disease, there are likely to be some symptoms.

Some common symptoms of myeloma

• Bone pain – usually in the back, ribs, hips or skull.
• Easily broken bones – usually without a cause, often involving the ribs or spine.
• Frequent infections or fevers – usually without an obvious cause. This occurs due to the abnormal immunoglobulins.
• Tiredness, rapid heart rate, shortness of breath, pale skin – symptoms of a low red blood cell (RBC) count, anaemia.
• Bruising and bleeding easily – due to a low platelet count.
• Feeling sick, drowsy, or confused – caused by elevated blood calcium.
• Changes to your urination habits – due to kidney damage caused by the myeloma.

Diagnosis of Myeloma

Myeloma is diagnosed from several tests:

• Medical history and physical exam
• Blood tests – full blood count (FBC), kidney and liver function, electrolytes, serum free light chain, cytogenetics, beta-2 microglobulin, albumin, lactate dehydrogenase (LDH)
• Urine tests
• Bone marrow biopsy
• Imaging tests – may include a skeletal survey, computed tomography (CT) scan, positron emission tomography (PET) scan, magnetic resonance imaging (MRI)

Active myeloma

The SLiM-CRAB criteria are used to work out if you have active myeloma that needs treatment.

SLiM-CRAB:

• S – sixty percent (60%) or more abnormal plasma cells in the bone marrow
• Li – light chains, high levels in the blood
• M – MRI with more than one bone abnormality
• C – calcium, high levels in the blood
• R – renal (kidney) damage
• A – anaemia, low red blood cell count
• B – bone lesions or fractures

Types of Myeloma:

Types of myeloma are classified based on the type of paraprotein produced by the myeloma cells.

Typical myeloma

Typical myeloma is the most common type of myeloma and is often referred to as just myeloma. This type of myeloma can be classified by the paraprotein (immunoglobulin) it produces. They are made up of one type of heavy chain and one type of light chain. There are 5 types of heavy chain immunoglobulins – IgG, IgA, IgD, IgE, IgM.
There are two types of light chain immunoglobulins:

• Kappa
• Lamba

In typical myeloma, the heavy chain is bound to the light chain. It is most often present in the blood but not the urine. Blood tests are a good way to monitor this type of myeloma. When the myeloma is active, there will be a rise in the paraprotein level. When the myeloma is responding to treatment, there will be a decrease in the paraprotein level. It is normal for the paraprotein to fluctuate a little bit. A small rise does not always mean that more or different treatment is needed.

Light chain myeloma

Light chain myeloma occurs in about 15% of people with myeloma. It is also known as Bence Jones myeloma. In light chain myeloma, myeloma cells only produce the light chain part of immunoglobulin. Not the heavy chain part. This is mostly detected in the urine. Small increases in the number of light chains in the blood can be detected through a blood test. This is called a serum free light chain test. This test can be used to see how you are responding to treatment. It is also used to look at the kappa and lamba light chain ratio. Everyone will have some free light chains in their blood. When these rise above normal levels, monitoring is required.

Non-secretory myeloma

Non-secretory myeloma occurs in about 3% of people with myeloma. This type of myeloma has no measurable paraprotein. It cannot be found in a blood or urine test. It can be hard to detect and monitor. It is often found on routine bloods tests for another health problem. Bone marrow biopsies and PET scans are used to diagnose and monitor this type of myeloma.

Precancerous conditions that can lead to myeloma:

Monoclonal gammopathy of undetermined significance (MGUS)

• MGUS is a disorder of the plasma cells.
• People with MGUS produce an abnormal protein called an M-protein rather than antibodies.
• The M-protein can build up in your blood stream and urine.
• The M-protein reduces your body’s ability to fight infection.
• MGUS doesn’t require any treatment, but monitoring is recommended.
• About 20% of people with MGUS develop myeloma.

Smoldering myeloma

• Smoldering myeloma is an early sign that you may develop myeloma after some time.
• There are usually no symptoms that affect you.
• People often learn they have smoldering myeloma from a blood test.
• Smoldering myeloma is managed by monitoring for signs and symptoms of active myeloma.
• Smoldering myeloma usually affects people over 60.
• 10% of people who have smoldering myeloma may develop active myeloma during the five years after diagnosis.

Solitary plasmacytoma

• Solitary plasmacytoma happens when plasma cells turn into abnormal cells, multiply and become a tumor that affect your bones.
• It only appears in one spot.
• It is often treated with radiotherapy.
• Approximately 50% of people with solitary plasmacytoma will develop myeloma.

Extramedullary plasmacytoma

• Extramedullary plasmacytoma happens when plasma cells turn into abnormal cells, multiply and become a tumor that affects the soft tissue.
• It often affects the tissue of your upper respiratory tract.
• It can be treated with surgery, chemotherapy, or immunotherapy.
• About 15% of people will go on to develop myeloma.

Prognosis of Myeloma

Myeloma is a treatable blood cancer, currently there is no cure. Your prognosis will include your type of myeloma and your overall health. Your treatment team will discuss prognosis and treatment options with you.

Treatments for Myeloma

Your haematologist will recommend treatment based on:

• Your diagnosis
• Age
• Other health conditions
• Physical condition
• Your wishes

Active treatment usually involves a combination of medications. This is because each act on myeloma cells in different ways. The aim of treatment is to:

• Reduce the amount of myeloma in the body
• Control any symptoms you are experiencing
• Keep the myeloma under control for as long as possible
• Improve your quality of life
• Prolong your life

Active monitoring

Active monitoring (watch and wait) involves regular blood tests and general health checks. No intervention is needed unless you develop signs and symptoms to suggest the myeloma is progressing. People with smouldering myeloma and MGUS are generally actively monitored.

Corticosteroids

Most myeloma treatment regimens use steroids. They can be used on their own. Most commonly they are given with chemotherapy, targeted therapy or immunotherapy.

Steroids can:

• Actively kill myeloma cells.
• Help other myeloma treatments be more effective.
• Act as an anti-inflammatory for people with myeloma bone disease.
• Act as an anti-nausea.
• Manage allergic type reactions to other myeloma medications.

During active treatment you will likely receive many courses of steroids. Dexamethasone and prednisolone are two types of steroids used in myeloma treatments. Dexamethasone is a strong steroid that is very good at killing myeloma cells. It has some side effects that can be hard to manage. Prednisolone also kills cancer cells, generally the side effects are better tolerated.

The main side effects of dexamethasone and prednisolone are:

• Stomach pain
• High blood sugar levels
• Mood changes
• Difficulty sleeping
• Fluid retention
• Energy changes
• Increased appetite and weight gain

Speak with your treatment team if you are experiencing any of these side effects.

Targeted therapy

Targeted therapy is designed to attack specific genetic abnormalities in cancer cells to stop the cancer cell from growing. Unlike chemo, targeted therapy only affects the cells that have the abnormality. You may be prescribed a targeted therapy called a proteasome inhibitor. These are often given in combination with other medications.

Proteasome inhibitors – bortezomib, ixazomib, carfilzomib are examples of proteasome inhibitors. These work by:

• Breaking down excess proteins in cells to stop growth and development.
• Blocking the proteasomes so that proteins build up in the cell and the cell dies.
• Are given either subcutaneously (under the skin), intravenously (IV) or orally.

Immunotherapy

Immunotherapy uses the immune system to recognise cancer cells and destroy them. There are two categories of immunotherapies given in myeloma:

Monoclonal antibodies act on a specific marker on a cell

• Daratumumab and Elotuzumab are examples of monoclonal antibodies given for myeloma.
• Daratumumab acts on monoclonal anti-CD38 antibody.
• It targets the CD38 protein on myeloma cells, so the immune system recognises it and kills the cell.
• Elotuzumab acts on a myeloma cell protein called SLAMF7. It stimulates your immune system to recognise and kill myeloma cells.
• These treatments are given in combination with either chemotherapy or other targeted therapies and steroids.

Immune system modulators work in several ways

• Thalidomide, lenalidomide, pomalidomide are examples of immune system modulators given for myeloma.
• They stimulate the immune system to attack and destroy cancer cells.
• They directly kill and stop the growth of cancer cells.
• They can block the growth of new blood vessels that supply cancer cells.
• They are given in combination with either chemotherapy or other targeted therapies.

Chemotherapy

Chemotherapy treatment for myeloma is often combined with other medications such as corticosteroids, immunotherapies or proteasome inhibitors. Common chemotherapies used to treat myeloma include:

• Melphalan
• Doxorubicin
• Cisplatin
• Cyclophosphamide

Chemotherapy for myeloma can be given through a drip into the vein (intravenous) or by taking a tablet. It is possible to have lots of side effects when you are having chemotherapy. Each chemo has different risks. Ask your treatment team about the specific risks of the chemo they are suggesting you have. Some more well-known side effects of chemo are:

• Nausea and vomiting
• Constipation and diarrhoea
• Losing interest in food and eating
• Chemo brain
• Tiredness that you can’t shake
• Infection

Read about how to manage some of these side effects. Tell your treatment team if you are not feeling well or are not coping.

Stem cell transplant

An autologous stem cell transplant is sometimes used to treat people with myeloma. It is a treatment that restores stem cells after high dose chemotherapy. An autologous stem cell transplant means that you receive your own stem cells. An allogeneic stem cell transplant may sometimes be used to treat myeloma. The stem cells you receive in an allogeneic transplant are from a donor. Your treatment team will let you know if this is an option for you.

For more information go to: Stem cell transplants – Leukaemia Foundation

Radiation therapy (Radiotherapy)

Radiation therapy is a local treatment that uses high energy rays to kill or damage cancer cells. It can be used to treat myeloma and plasmacytoma’s that are causing problems like pain and bone fractures.

Radiation therapy is used in myeloma for:

• Pain relief – help reduce bone pain. Shrinks the amount of myeloma cells in the bone and slows down bone damage.
• Targeting specific areas – without affecting the whole body. It treats growths or lumps in specific spots.
• Combination treatment – given with other treatments to control the disease and manage symptoms.
• Preventing complications – prevents further damage to bones, especially the spine.

Supportive care

Supportive care controls symptoms of myeloma and side effects of treatment. It aims to improve your quality of life. Supportive care does not aim to treat the disease. It can help with symptoms such as tiredness, breathlessness, bruising or bleeding and high blood calcium. Supportive care may include:

• Blood transfusions
• Platelet transfusions
• Bisphosphonates

For more information go to: Supportive care – Leukaemia Foundation

Bisphosphonates are drugs that are used to strengthen and protect the bones. People with myeloma are at a high risk for developing bone fractures. This is because the balance between building new bone and bone loss is uneven. People with myeloma experience more bone loss than bone growth.

This leads to;

• Osteoporosis
• Lytic lesions (holes in bones)
• Bone pain
• High levels of blood calcium
• Bone fractures

Regular treatment with bisphosphonates can reduce the risk of:

• Bone pain
• High levels of blood calcium
• Bone fractures

Bisphosphonate therapies include:

• Zoledronic acid – 15 minute infusion through a vein
• Pamidronate – 90 minute infusion through a vein
• Clodronate – tablets taken twice a day

Bisphosphonates have some side effects including:

• Flu like symptoms
• Muscle and joint aches and pains
• Low blood calcium, phosphate and magnesium levels
• Osteonecrosis of the jaw (ONJ)

You’ll need to have a dental assessment and any dental treatment before you start bisphosphonates. You’ll also need regular dental reviews and blood tests while you have treatment. Tell your treatment team if you experience any side effects.

Monitoring myeloma

Your treatment team will monitor your myeloma depending on your type of myeloma and the aim of treatment. Blood tests are taken frequently to see how you are responding to treatment. Your haematologist may be looking for the number of light chains in the blood or the kappa lamba light chain ratio. You may also have bone marrow biopsies, bone scans, PET scans and CT scans. After a period of remission your myeloma may relapse. This news can be difficult to hear. Your treatment team will discuss your options with you. It’s important to seek support from those closest to you. To speak to a Leukaemia Foundation Healthcare Professional call 1800 620 420 or via email at info@leukaemia.org.au.

Living with myeloma

Myeloma treatments can be good at slowing down the disease, controlling symptoms and improving your quality of life. Living with myeloma is different for everyone. It’s important to seek support from your loved ones so they can help you along your treatment journey. The Leukaemia Foundation has resources to support you.

• How we can help
• Webinars and support groups
• Online Blood Cancer Support Service