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This article waslast modified on 23 October 2018.

Myeloma is a cancer that develops in cells of the bone marrow called plasma cells. Plasma cells develop from B lymphocytes and are an important part of the immune system. Their primary function is to produce antibodies – targeted immunoglobulin proteins that help protect the body against infections. Normally, plasma cells are produced as needed. When B cells are exposed to pathogens, they mature into plasma cells and begin to produce antibodies. They share space in the bone marrow with maturing red blood cells (RBCs), platelets, and several types of white blood cells (WBCs). Sometimes, however, a plasma cell may become malignant and begins to divide uncontrollably, forming tumours in the bone marrow, eroding the surrounding bone and producing producing soft spots and holes known as lytic lesions. Myeloma can develop wherever there is bone marrow, including the pelvis, spine and ribcage. As it can occur in several places in the body, it is often called multiple myeloma.

Since the malignant cells are derived from a single plasma cell, they all produce an identical antibody – an abnormal monoclonal immunoglobulin (also termed an M-protein) that is released into the blood and sometimes excreted in the urine. The abnormal antibody does not work properly and is not able to fight infections while the proliferation of malignant cells can affect the production of normal antibodies (immunosuppression), causing susceptibility to infection.

Normally, the body makes five different types of immunoglobulins - IgG, IgA, IgM, IgE and IgD - that have slightly different immune system functions. Each type of immunoglobulin is composed of four protein chains - two identical heavy (long) protein chains and two identical light (shorter) protein chains. The light chains consist of one of two different types called kappa and lambda. Within a plasma cell, two heavy chains of one type and two light chains of one type become attached to form one intact immunoglobulin. Each particular plasma cell will produce only one type of immunoglobulin.

In patients with multiple myeloma, the malignant plasma cells produce only one type of intact (whole) immunoglobulin in large amounts. However, in about 75% of myeloma patients, the balance in production of light and heavy chains is disturbed and light chains are produced in excess. The surplus free light chains are released into the bloodstream and, because they are relatively small molecules, they are filtered by the kidneys and excreted into the urine, as a protein known as Bence-Jones protein. Rarely, the monoclonal protein produced consists only of light chains or, very rarely, heavy chains. Though the type of M protein produced by malignant cells may vary from one patient to the next, within one particular patient it is always the same since it is produced by identical or cloned plasma cells.

The type of myeloma a patient has is often referred to by the type of M protein produced, whether an intact immunoglobulin or light chain. Patients with IgG and IgA myelomas are the most common, with IgG types comprising about 60-70% of myelomas and IgA types making up about 20% of myelomas. Cases of IgE and IgD are only rarely reported. Some patients who produce monoclonal IgM may have a related but different condition called Waldenstrom‘s macroglobulinaaemia.

Monoclonal Gammopathy of Undetermined Significance (MGUS):
Sometimes people will produce abnormal amounts of identical copies of the same immunoglobulin (also known as monoclonal gammopathy) but not have any of the symptoms or complications of multiple myeloma. This condition is referred to as monoclonal gammopathy of undetermined significance or MGUS. Often, this condition is only discovered when routine tests reveal abnormal amounts of protein in the blood. About 20 to 30% of individuals with will go on to develop myeloma or some other related disease such as lymphoma. Generally, these patients do not require any treatment, but they are closely monitored. Some of the tests used to diagnose and/or follow multiple myeloma are used to monitor patients with MGUS.


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About Multiple Myeloma
  • Symptoms and Signs

    Many patients with multiple myeloma may show no symptoms for many years. Eventually, most patients develop some evidence of the disease either related to weakened bones (bone pain), decreased numbers of red or white blood cells (anaemia, infections), or kidney failure. As bones weaken, soft spots and fractures may develop. Destruction of the bone frequently increases the level of calcium in the blood, leading to symptoms of hypercalcaemia such as loss of appetite, nausea, thirst, fatigue, constipation, and confusion. A decrease in the number of normal white blood cells, red blod cells and platelets can result in recurrent infections, anaemia, bleeding, and bruising. Bence-Jones proteins can lodge in the kidneys and may permanently damage them. In some cases, an increase in the thickness (viscosity) of the blood may lead to headaches.

    Multiple myeloma is relatively uncommon. According to Cancer Research UK, Myeloma is the 17th most common cancer in the UK (2009 data), accounting for around 1.5% of all new cases of malignancy. This equates to around 8 cases for every 100,000 people in the UK population. The cause of multiple myeloma is not yet known. The risk of developing it increases with age, with the majority of cases being diagnosed in patients 60 years or older. There is evidence of increased risk associated with a decrease in immune system function (e.g. HIV, post organ transplant). It has been suggested that occupational exposure to certain chemicals may increase risk but the International Agency for Research on Cancer (IARC) states that the evidence is limited. Genetic factors may also play a role; people with a parent, brother, sister, or child with myeloma or MGUS are 2 or 3 times as likely to develop myeloma or MGUS compared to people with no close family members with these illnesses.


  • Tests

    The goals of testing for multiple myeloma are to diagnose the condition, determine its severity and spread, monitor its progress, detect complications as they arise and monitor the effectiveness of treatment. There is no one single test that can diagnose multiple myeloma. Typically, the disease is diagnosed using a combination of patient’s signs and symptoms, medical history, physical examination, laboratory tests, and/or imaging tests.

    Laboratory Tests
    Multiple myeloma may first be suggested during routine blood testing, with the finding of an abnormal total protein level, an elevated calcium level, a low white or red blood cell count, an elevated erythrocyte sedimentation rate (ESR) and / or moderate to large amounts of protein in the urine. Findings such as these may raise suspicions but are not diagnostic as similar abnormalities may be seen with a variety of other conditions. They simply indicate the need for further testing.

    Tests used as a follow-up to help diagnose the disease may include one or more of the following:

    Serum Protein Electrophoresis: This test is used to diagnose and monitor multiple myeloma. Protein electrophoresis separates the proteins in a blood sample into several groups based on their electrical charge and size. In most patients with multiple myeloma, large amounts of an abnormal immunoglobulin protein (M-protein) will show up as an abnormal band on the electrophoresis strip. The amount of normal immunoglobulins in the sample may be visibly decreased. Usually, both a blood and a urine sample will be tested during the diagnosis of multiple myeloma because some proteins, such as the Bence Jones proteins (free light chains), may not show up in significant quantities in blood samples, while those with only intact immunoglobulins may not have the abnormal protein in urine.

    Immunofixation: is a technique used to identify the specific type of abnormal protein that is being produced by the malignant plasma cells. The amount of protein produced may vary throughout the course of the disease, but the type will remain the same.

    Bence-Jones protein (free light chains) can be detected in the urine of some patients with multiple myeloma. Usually the qualitative detection of Bence-Jones protein in an early morning urine sample is adequate, though occasionally, quantitation in a 24-hour urine collection may be requested.

    Serum free light chains (SFLC):This test measures the amount of free light chains in the blood. Even in normal circumstances (and for unknown reasons), plasma cells produce an excess of light chains compared to heavy chains and there is usually a small amount of light chains that do not become incorporated into intact immunoglobulins. These remain as free light chains and are released into the bloodstream. Most patients with multiple myeloma produce increased amounts of either kappa or lambda free light chains, which can be measured in blood. Consequently, the ratio of kappa to lambda light chains is abnormal in most patients and is a sensitive indicator for this disease. This test may be used to monitor progression and/or treatment.

    Quantitative Immunoglobulins: Each of these tests measures amounts of a different type of immunoglobulin. The multiple myeloma protein will be an IgG, IgA or, rarely, an IgD or IgE immunoglobulin. Patients with a monoclonal IgM immunoglobulin may have a related but different disease (Waldenstrom’s macroglobulinaemia). IgG, IgA, and IgM may be requested to help diagnose multiple myeloma and to monitor the course of the disease and its effect on the production of normal immunoglobulins.

    Bone marrow aspiration and biopsy: Multiple myeloma is a disease of the bone marrow. Patients usually require a bone marrow evaluation to confirm the diagnosis, evaluate how many malignant plasma cells are present in the marrow, and to what degree they have affected the production of normal white or red blood cells and platelets.

    Beta2-microglobulin: is a protein on the cell surface of myeloma and other cells. Increased levels may indicate a poorer prognosis, but this protein may also be elevated in other diseases.

    Other Laboratory Tests
    Other tests that may be done as part of an initial diagnostic workup, to monitor the progress of the disease, and to help detect and address complications include renal profile, calcium level, uric acid level and full blood count.

    Non-Laboratory Tests
    The large numbers of plasma cells being made in the bone marrow can cause damage to the hard outer covering of the bones. Your doctor will ask you to have X-rays of all your long bones, and your spine, pelvis and skull, to find any areas of damage. This is termed a skeletal survey.

    MRI (Magnetic Resonance Imaging) can be more sensitive than X-ray for evaluating bone destruction and is occasionally resorted to.


    The stage of a cancer tells your doctor how far it has grown or spread. Staging is based on information obtained from the tests and scans you have when diagnosing your myeloma, such as abnormal immunoglobulin being produced, the serum calcium level, the amount of normal proteins and ß-2 microglobulin in blood and the extent and severity of the bone damage. Staging helps to determine a patient’s prognosis and allows your specialist plan the treatment that is most appropriate for you.


  • Treatment

    At this time, multiple myeloma is not considered curable, although current treatments may produce a complete remission in some patients (disappearance but not cure of the disease). The goals of treatment are to relieve pain and other symptoms, to slow the progress of the disease, and to detect and minimise complications as they occur. Doctors generally recommend that patients with multiple myeloma stay as active as possible to help preserve the calcium in their bones and drink plenty of fluids to help with kidney function. Complications such as infections, anaemia and bleeding should be promptly addressed with measures such as antibiotics and, when necessary, transfusions. Patients who do not have significant symptoms are monitored but may not receive any treatment. In early multiple myeloma, the side effects of the available treatments frequently outweigh the benefits.

    Chemotherapy, steroids and biological therapies are the main treatments for myeloma. Radiotherapy is also used to help control pain. Stem cell transplant and Thalidomide and related agents are more recent therapeutic options. You may also be prescribed bisphosphonates to help prevent bone damage and relieve pain. If you are fit enough, your specialist may suggest intensive treatment using high dose chemotherapy with a bone marrow or stem cell transplant.

    Your doctor may suggest a treatment called plasmapheresis if the level of abnormal immunoglobulin protein is too high in your blood. Too much protein in the blood can make it too thick and plasmapheresis can remove the excess protein.