Myeloma, also known as multiple myeloma, is a rare type of cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs that develops from white bloodthe red bodily fluid that transports oxygen and other nutrients around the body cellsthe basic structural and functional unit of all living things in bone marrowsoft, spongy tissue found in bones that makes blood cells. More specifically, they develop from plasma cells, which produce large, Y-shaped antibodies/immunoglobins (Ig) to help the body fight infectiona condition where harmful pathogens, such as bacteria, viruses or parasites, have entered the body. 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 plateletssmall disc-shaped blood cells that clump together to form clots to stop bleeding). 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 prognosisto predict how a disease/condition may progress and what the outcome might be 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 tissuetissue/the material that joins, holds up or surrounds inside body parts such as fat, muscle, ligaments and lining around joints, but can also develop in the liver, kidneys, lymph nodessmall bean-shaped structures that filters harmful substances from lymph fluid, central nervous system (CNS), breast, pleuraa thin layer of tissue covering the lungs and the wall of the interior chest cavity and pericardiumfluid-filled sac membrane that surrounds and protects 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 tissuea group of cells that work together to perform a function or within bones. It may present as a solitary massa growth of cells that come together to make a lump, may or may not be cancer 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, metastasiswhen the cancer has spread to other parts of the body, also known as mets, and how the cancer cells look under the microscope. Stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 (kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body) damage.
- A – Anaemiaa condition where there aren't enough red blood cells in the blood, causing fatigue, weakness and pale skin and affecting how the body responds to infection (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 tumoura tissue mass that forms from groups of unhealthy cells has been staged and graded, your doctor may recommend genetic testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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:
- Chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Immunomodulatory therapymedication used to modify the body's immune system.
- Proteasome inhibitorsmedication that inhibits the action of proteasomes, which are substances that break down proteins in the body.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation.
- Stem cell transplanta procedure that involves replacing unhealthy blood-forming cells (stem cells) with healthy stem cells.
- Bone marrow transplanta procedure that involves replacing unhealthy bone marrow with healthy bone marrow.
- Biphosphonatesmedication that is used to treat and/or prevent bone disease.
- Immunoglobulin replacement therapya procedure that involves administering antibodies collected from plasma donations either into the vein (intravenously) or under the skin (subcutaneously).
- Plasma exchangea procedure to remove and replace plasma in the blood.
- Interferon therapya treatment that uses synthetic versions of proteins made by the body to fight cancer.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
Risk factors
While the causes of myeloma remain unknown, some potential riskthe possibility that something bad will happen 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.
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.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental.
- Anaemia.
- Easy bruising or bleeding.
- Dyspneadifficulty breathing, shortness of breath.
- Tachycardiaa rapid heart rate; clinically defined as a rate of more than 100 beats per minute.
- Kidney (renal) problems.
- Heavy nose bleeds.
- Nauseato feel sick or likely to vomit.
- 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
If your doctor suspects you have a myeloma, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results and refer you to a specialist for treatment:
- Physical examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Urine teststesting done to measure the levels of certain substances in the urine.
- Imagingtests that create detailed images of areas inside the body scans to check for bone damage, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow..
- Biopsyremoval of a section of tissue to analyse for cancer cells.
