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 it produces. They are made up of one type of heavy chain and one type of light chain.

There are five types of heavy chain immunoglobulins (Ig):

• 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 to form the paraprotein. 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. However, 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 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 occurs in about 3% of people with myeloma. This type of myeloma produces no measurable paraprotein, so it cannot be detected in blood or urine tests, making it difficult to diagnose and monitor. Therefore, bone marrow biopsies and PET scans are used to diagnose and monitor this type of myeloma.

• 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.

• Is an early sign that you may develop myeloma after some time.
• Does not usually present many symptoms that affect you.
• Can be discovered through a blood test.
• Is managed by monitoring for signs and symptoms of active myeloma.
• Tends to affect people over 60.
• May develop into active myeloma during the five years after diagnosis for 10% of people with smouldering myeloma.

• Happens when plasma cells turn into abnormal cells, multiply and become a tumour that affect your bones.
• Appears only in one spot.
• It is often treated with radiotherapy.
• Can develop into myeloma for approximately 50% of people with solitary plasmacytoma.

• Happens when plasma cells turn into abnormal cells, multiply and become a tumour that affects the soft tissue.
• Tends to affect the tissue of your upper respiratory tract.
• Can be treated with surgery, chemotherapy, or immunotherapy.
• Could develop into myeloma for approximately 15% of people.

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.

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 medication
• 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. On the other hand, it has some side effects that can be hard to manage. While 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 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 inhibitor examples

• bortezomib
• ixazomib
• carfilzomib.

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
• being given either subcutaneously (under the skin), intravenously (IV) or orally.

Side effects from targeted therapies tend to be different to chemo side effects. If you’re having more than one type of drug, you may have a few different side effects at different times. Your treatment team will talk to you about what you might expect.

You can read more about targeted therapy and specific side effects on this webpage Immunotherapies and targeted therapies | Leukaemia Foundation

Immunotherapy uses the immune system to recognise cancer cells and destroy them. Monoclonal antibodies and immune system modulators, for example, are two types of immunotherapies given in myeloma. These can be given in combination with other medications.

Monoclonal antibodies

• Daratumumab and Elotuzumab are examples of monoclonal antibodies given for myeloma.
• Daratumumab acts on monoclonal anti-CD38 antibody.
• Daratumumab 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.
• Elotuzumab stimulates your immune system to recognise and kill myeloma cells.

Immune system modulators

• Thalidomide, lenalidomide, and 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.

Side effects from immunotherapies tend to be different to chemo side effects. If you’re having more than one type of drug, you may have a few different side effects at different times. Your treatment team will talk to you about what you might expect.

You can read more about immunotherapy and specific side effects on this webpage Immunotherapies and targeted therapies | Leukaemia Foundation

Chemotherapy (chemo) 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.

Chemo is given through a drip into the vein (intravenous) or by taking a tablet. It is therefore possible to have lots of side effects when you are having chemo. Each chemo has different risks. Ask your treatment team about the specific risks of the chemo they have prescribed for you.

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.

Myeloma can be treated with an autologous stem cell transplant. 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. There are times when myeloma is treated with an allogeneic stem cell transplant. 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 visit: Stem cell transplants – Leukaemia Foundation

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 plasmacytomas that are causing problems like pain and bone fractures.

Radiation therapy is used in myeloma to:

• relieve and reduce bone pain
• shrink the amount of myeloma cells in the bones to slow down bone damage 
• target specific growths, lumps or areas that need treatment without affecting the whole body. 
• treat in combination with other treatment 
• prevent complications like further bone damage.

For more information visit: Radiation therapy – Leukaemia Foundation

Supportive care controls symptoms of myeloma and side effects of treatment. It aims to improve your quality of life but does not intend 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

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. As a result, 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).
  • read more about ONJ on our supportive care webpage.

You need to have a dental assessment and any dental treatment before starting bisphosphonates. Regular dental reviews and blood tests might also be required during treatment. Tell your treatment team if you experience any side effects.