Myeloma, also known as multiple myeloma, is a rare type of cancer that develops from white blood cells in bone marrow. More specifically, they develop from plasma cells, which produce large, Y-shaped antibodies/immunoglobins (Ig) to help the body fight infection. In patients with myeloma, abnormal plasma cells become myeloma cells. 

Blood is the bodily fluid of the circulatory system that provides nutrients and oxygen to our tissues, and helps remove waste from our bodies. There are three primary types of blood cells produced in the inner, spongy portion of the bone (bone marrow) from stem cells (immature blood cells that develop into either red blood cells (RBCs), white blood cells (WBCs) or platelets). RBCs, or erythrocytes, are responsible for providing oxygen to the tissues in our body, as well as transporting carbon dioxide to the lungs to be exhaled. WBCs are responsible for fighting infection and disease in the body. Plasma cells are a type of B lymphocyte (a type of mature WBC) that produces a type of protein known as antibodies or Ig in response to foreign bacteria, viruses, or other harmful substances in the body. Platelets are blood cells that play a major role in blood clotting (or coagulation), which is an important process that helps reduce blood loss after an injury. As myeloma cells grow, bone marrow is prevented from developing normal levels of RBCs, WBCs and platelets.

Immunoglobulins are composed of four chains two identical heavy chains and two identical light chains. The heavy chains are categorised into five different subtypes (G, A, D, E and M), which all have different roles within our immune system. The light chains are categorised into two different subtypes (kappa and lambda), which help the binding of antibodies to what they are fighting. Each immunoglobulin has only one type of heavy chain, and one type of light chain. Myelomas can be categorised based on which chains are abnormally produced.  

Myeloma is more common in males, and is generally diagnosed over the age of 60. However, anyone can develop this disease.

Types of Myelomas 

There are different types of myelomas, which are categorised by the stage of disease, the types of immunoglobulins involved, and whether patients are symptomatic.

Subtypes based on Symptoms

Myelomas can be categorised based on whether or not there are symptoms.

Active Myelomas (symptomatic myelomas)

Active myelomas are symptomatic forms of myeloma. Patients with active myelomas often require immediate treatment. 

Smouldering Myeloma (asymptomatic myeloma)

Smouldering myeloma is a very early-stage subtype of myeloma, where myeloma cells are present in bone marrow, but the patient is asymptomatic. People diagnosed with this type of disease usually don’t need treatment right away, but may be required as the cancer progresses.

Subtypes based on Immunoglobulins 

Myelomas can be categorised based on which immunoglobulins are abnormal. In general, IgG myeloma is most common, followed by IgA myeloma. IgD, IgE and IgM myeloma are quite rare. These myelomas can have either the kappa or lambda light chains. 

Light Chain Myeloma

Light chain myeloma, also known as Bence-Jones myeloma, is a rare subtype of myeloma that occurs when myeloma cells produce incomplete immunoglobulins with only light chains present. When this occurs, the light chains are excreted in the urine and are referred to as Bence-Jones proteins. This subtype if often aggressive, and may not have as good of a prognosis as other types of myelomas.

Non-secretory Myeloma

Non-secretory myeloma is a very rare form of myeloma that occurs when very little amounts of abnormal immunoglobulins are produced. While it can produce the same symptoms as other types of myeloma, it can be very difficult to diagnose. Non-secretory myeloma is often less aggressive than other types of myeloma.

Extramedullary Myeloma 

Extramedullary myeloma is a rare form of myeloma that occurs when abnormal plasma cells develop outside of the bone marrow. The symptoms and treatment of this subtype often depend on where the tumours have developed. This subtype generally develops in the skin or soft tissue, but can also develop in the liver, kidneys, lymph nodes, central nervous system (CNS), breast, pleura (lining of the lungs) and pericardium (fluid-filled region surrounding the heart). Extramedullary myelomas are often aggressive, and may not have as good of a prognosis as other types of myeloma.

Associated Conditions

There are conditions that may develop into multiple myeloma if left untreated.

Monoclonal gammopathy of undetermined significance (MGUS)

Monoclonal gammopathy of undetermined significance (MGUS) is a non-cancerous, associated condition related to myeloma. MGUS is an asymptomatic condition, and does not often require treatment other than regular follow-ups with their doctor. Some patients with MGUS may develop myeloma.

Plasmacytoma

Plasmacytomas are a cancerous condition classified as abnormal plasma cells that grows within soft tissue or within bones. It may present as a solitary mass or in multiple areas of the body, and can develop into multiple myeloma if left untreated. For more information on plasmacytomas, please refer to the Rare Cancers Australia Plasmacytoma page.

Treatment

If a myeloma is detected, it will be staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body) and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you.

Cancers can be staged using the revised international staging system (R-ISS), which is often divided into three stages based on the levels of beta-2 microglobulin (BM2) (a protein produced by myeloma cells), albumin (liver protein that indicates overall health), lactate dehydrogenase (LDH) (an enzyme released when cell damage occurs) and genetic information (any chromosomal abnormalities that may increase rick of disease progression) in the blood. These stages are:

• Stage I: low levels of B2M, high levels of albumin, normal LDH levels and no high-risk chromosomal abnormalities.
• Stage II: Not stage I or III, with myeloma cells present.
• Stage III: high levels of B2M, high LDH levels and/or high-risk chromosomal abnormalities. 

Doctors may also use SLiM-CRAB criteria to determine which treatment options may have the best chance of success, as well as stage of disease. The SLiM criteria consists of three specific biomarkers (properties of cells that are used to measure the presence or progression of disease), while the CRAB criteria are the common indicators of myeloma which are used to determine stage of disease. The SLiM-CRAB criteria involves:

• S – 60% of plasma cells in the bone marrow are abnormal (plasmacytosis).
• Li – Light chain ratio (high levels of ‘light chains’ in the blood, which are short chains of the paraproteins produced by myeloma cells).
• M – MRI lesions (bone abnormalities >5mm observed on an MRI).
• C – Calcium levels are elevated in the blood.
• R – Renal (kidney) damage.
• A – Anaemia (low levels of RBCs in the blood).
• B – Bone pain and/or damage (areas of damage – or lytic lesions – and/or bone loss – osteoporosis). 

Once your tumour has been staged and graded, your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you. 

Treatment is dependent on several factors, including location, stage of disease and overall health. 

Treatment options for active myelomas may include:

• Chemotherapy.
• Radiotherapy.
• Immunomodulatory therapies. 
• Proteasome inhibitors.
• Monoclonal antibodies.
• Cortico-steroids. 
• Stem-cell and/or bone marrow transplant.
• Biphosphates.
• Immunoglobulin replacement therapy.
• Plasma exchange.
• Interferon therapy.
• Clinical trials.
• Palliative care.

For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.

Risk factors

While the causes of myeloma remain unknown, some potential risk factors have been identified for this disease:

• Genetic abnormalities.
• Exposure to certain chemicals, such as dioxin.
• Exposure to high levels of radiation treatment, such as from radiation therapy or from working in a nuclear transplant.
• People who have been diagnosed with MGUS.
• Family history of myeloma (rare). 

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Early symptoms

Patients with early-stage myeloma may be asymptomatic. As the tumour progresses, some of the following symptoms may appear:

• Bone pain, most commonly in the back or ribs.
• Easily broken bones.
• Persistent infections.
• Unexplained fever.
• Fatigue.
• Anaemia.
• Easy bruising or bleeding.
• Unexplained shortness of breath.
• Unexplained heart racing.
• Kidney (renal) problems.
• Heavy nose bleeds.
• Nausea.
• Drowsiness.
• Confusion.
• Abnormal blood counts (unusual RBC, WBC and/or platelet levels).

Not everyone with the symptoms above will have cancer, but see your GP if you are concerned.

Diagnosis/diagnosing

If your doctor suspects you have a myeloma, they will order a range of diagnostic tests to confirm the diagnosis, and refer you to a specialist for treatment.

Physical examination

Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.

Urine & blood tests

Urine and blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:

• General blood test to assess overall health.
• Full blood count, which measure the levels of red blood cells, white blood cells and platelets.
• Serum analysis, which involves a serum protein electrophoresis test to measure the level of paraprotein in your blood.
• Genetic testing to check for any abnormalities, specifically changes in chromosomes 4, 13, 14 and/or 17.
• 24-hour urine test, which involves collecting urine samples over a 24 hour period and checking for the presence of the Bence Jones protein (the light-chain portion of a paraprotein).

Imaging tests

The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), ultrasound, bone scan and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis. 

Bone marrow aspiration

This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for abnormalities.

Biopsy

Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA), a core needle biopsy (CNB), or a trephine biopsy (removal of a small portion of bone for analysis). 

Prognosis (Certain factors affect the prognosis and treatment options)

While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage myelomas have a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis. 

References

• Cancer Australia
• Cancer Council Australia
• Leukaemia Foundation Australia

_{Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.}