Background Information Myeloma
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1 Myeloma FAST FACTS Myeloma, also known as multiple myeloma, is a type of cancer that develops from plasma cells which originate in the bone marrow 1 Myeloma is the second most common type of blood cancer 2 Just under 4,800 people in the UK are diagnosed with myeloma each year 3 Myeloma represents about 15% of all blood cancers 2 and 1.5% of all cancers (about 3 in every 200 people) 3 As a group, blood cancers make up about 20% of all cancers 2 Myeloma most commonly occurs in people later in life i.e. over the age of 60 2 It is twice as common in black populations as it is in white and Asian populations 3 Currently there is no known cure for myeloma but it can be effectively managed 4 Myeloma, also known as multiple myeloma, is a type of cancer that develops from plasma cells which originate in the bone marrow. Bone marrow is the spongy tissue found inside the inner part of some of our large bones. The bone marrow produces different types of blood cells. 5 Myeloma can develop wherever there are plasma cells, so it can be anywhere in the bone marrow, including the pelvis, spine and ribcage. As it can occur in several places in the body (the bones of the spine, skull, pelvis, ribs and around the shoulders and hips), it is often called multiple myeloma. 5 Plasma cells form part of the immune system. Normal plasma cells produce antibodies (also called immunoglobulins) to help fight infection. They make different antibodies for different infections. 5 In myeloma, malignant plasma cells (myeloma cells) in the bone marrow produce large amounts of an antibody known as paraprotein. Unlike normal antibodies, paraprotein has no useful function. The measurement of this paraprotein is one of the ways in which myeloma is diagnosed and monitored. 5 Most of the medical symptoms related to myeloma are caused by the build-up of myeloma cells in the bone marrow and presence of paraprotein in the blood. Common symptoms include: bone pain; fatigue; infection; bone fractures; anaemia; kidney damage. 5 Myeloma is relatively rare with approximately 4,000 new diagnoses each year. Between 14,000 20,000 people are currently living with myeloma in the UK. 5 It mainly occurs in people over the age of 60 and affects slightly more men than women. 2 Overall, about 70 out of every 100 people (70%) diagnosed with myeloma in England, Wales and Scotland live for at least a year after diagnosis. About 37 out of every 100 (37%) live for at least 5 years. It is estimated that between 15 and 19 people in every 100 (15 to 19%) will live for at least 10 years. 6 Diagnosis of Myeloma In order to diagnose myeloma, several tests and investigations need to be carried out. This is often a difficult and uncertain time for patients and their families. Myeloma is a very individual disease and results from these tests may vary from patient to patient. It is not enough just to make a diagnosis of myeloma; it is critical to have an accurate picture of the disease in each patient before an appropriate treatment plan can be developed. 5 There are three main tests that are carried out to confirm diagnosis of myeloma; paraprotein measurement, X-rays of skeleton (skeletal survey), and a bone marrow biopsy. 5 Paraprotein measurement As well as being important in diagnosing myeloma, changes in the paraprotein level are a good indicator of changes in the activity of the myeloma. For this reason, regular blood tests are done to measure paraprotein levels 5 1
2 X-Rays of skeleton As myeloma can damage the bones, one of the first investigations performed is a skeletal survey. This is a series of X-rays used to detect any old or more recent bone damage. Areas of bone damage show up on X-ray film as black shaded areas and are known as lytic lesions. Sometimes an even clearer picture of the bone is needed and patients may have an MRI (magnetic resonance imaging) or CT (computerised tomography) scan. MRI and CT scans can provide more detail and can identify areas of bone damage which may not show up on X-ray 5 A bone marrow biopsy A bone marrow biopsy involves putting a needle into a bone (usually the hip bone) to get a small sample of the bone marrow; this sample is collected under a local anaesthetic. This sample is then examined to count the number of plasma cells present in the bone marrow. Normal bone marrow has less than 5% plasma cells; bone marrow in patients with myeloma may have between 10% and 90% plasma cells. This test may also be done at the end of treatment. 5 Staging of Myeloma On completion of a wide range of tests, a doctor should have a clear and in-depth picture of the specific characteristics of a patient s myeloma. With this information, the myeloma is normally staged. Staging indicates the amount of myeloma and therefore reflects the expected outlook for individual patients. The most commonly used staging system is called the International Staging System (ISS), which classifies myeloma into three stages. 5 There is also an older staging system called the Durie-Salmon staging system, but this is now rarely used. 7 International Staging System (ISS) Stage 1 Stage 2 Stage 3 Early, low level of myeloma 5 (the level of the protein called beta 2 microglobulin (ß2-microglobulin or ß2-M) is less than 3.5 mg per litre. And the level of albumin in the blood is more than 3.5 grams per decilitre) 7 Active, moderate level of myeloma 5 (the levels of beta 2 microglobulin and albumin fall between those in stages 1 and 3) 7 Active, high level of myeloma 5 (the level of the protein beta 2 microglobulin is more than 5.5 mg per litre) 7 The ISS system uses two factors to predict potential response to treatment; beta 2 microglobulin level and albumin level, which can both be assessed by doing a simple blood test. To help identify patients with myeloma that may not be causing symptoms but which requires treatment, doctors may also use other criteria. The acronym CRAB describes these criteria: (C) calcium elevation, (R) renal (kidney) insufficiency, (A) anaemia and (B) bone abnormalities (lytic lesions or bone loss). 5 In classifying myeloma, a doctor will also check whether or not a patient has either repeat infections or thickening of blood due to large amounts of paraprotein (hyperviscosity). Doctors will then group patients as having either asymptomatic myeloma (myeloma without symptoms) or symptomatic myeloma (myeloma with symptoms). 7 Myeloma can respond very well to treatment. 5 Response to treatment can be referred to as a complete response (CR) or a partial response (PR). Complete response means that the cancer can't be detected on scans, X-rays, or blood tests, etc. 8 In practical terms, it means less than 5% of plasma cells in the bone marrow and no detectable paraprotein. 9 Partial response means that the treatment has killed some of the cells, but not all. 8 In practical terms, it means that there has been a greater or equal to 50% reduction of paraprotein in blood, and a greater or equal to 90% reduction in 24 hour urinary paraprotein. 9 If the cancer comes back or the level of paraprotein rises again, it is called relapsed myeloma or recurrent myeloma. 7 2
3 Current Treatment Options Various factors will determine treatment options when a patient is diagnosed with myeloma. For those patients considered to have Monoclonal Gammopathy of Undetermined Significance (MGUS) or smouldering myeloma, i.e. those with low levels of M paraprotein who do not have symptoms, the standard of care is no treatment. 5 If the myeloma is not causing symptoms (asymptomatic), the risks of having chemotherapy treatment will often outweigh the potential benefits. 10 These patients will usually be closely monitored for symptoms and clinical signs. 11 On the other hand, if the myeloma is causing symptoms at diagnosis, or has come back after previous treatment, then the doctor will talk to the patient about possible treatment options. 10 Treatment options for myeloma can be very effective in relieving its symptoms, prolonging survival and improving quality of life. However, treatment for myeloma is not curative. 11 There are now a number of different treatments for myeloma, which are used at different stages of the disease and in different combinations. These include chemotherapy, steroids, high dose chemotherapy and stem cell transplantation, and also treatments such as Velcade (bortezomib), Revlimid (lenalidomide) and Thalidomide. 5 Chemotherapy (doxorubicin, cyclophosphamide, melphalan and vincristine) The type of chemotherapy prescribed for myeloma patients depends on the individual and what is most suitable for them and their myeloma at any particular point in time. Chemotherapy works by destroying myeloma cells in the bone marrow, preventing them from being able to divide and reproduce. Chemotherapy drugs attack all rapidly dividing cells in the body. This includes the myeloma cells, but also may affect other rapidly dividing cells such as normal developing blood cells in the bone marrow, hair follicles and the lining of the mouth and the stomach. It is this that causes some of the side-effects of chemotherapy treatment. Cyclophosphamide and melphalan are usually given orally (by mouth in tablet form). Vincristine and Adriamycin (also called doxorubicin) are given intravenously (into a vein). 5 A course of treatment can vary in length depending on the type and / or combination of chemotherapy planned. Most courses last approximately 4 to 6 months. During this period, the patient will have a number of individual treatment cycles, each lasting approx 3 to 6 weeks. 10 A drawback of some myeloma treatments, particularly with chemotherapy drugs, is the inability to give high doses safely. This is because high doses are toxic to the blood-forming stem cells in the bone marrow and affect blood cell production. This results in blood counts falling to dangerously low levels, causing potentially life-threatening complications 12 therefore, patients should be monitored carefully and regular full blood counts should be taken. 10 Steroids (dexamethasone and prednisolone) Steroids are hormonal substances naturally produced in the body. There are many different types of steroids; those used in the treatment of myeloma are known as glucocorticoids. These steroids can suppress inflammation (thus helping to reduce the pain associated with myeloma) and the immune response. 13 While not everything is known about how steroids work, it is recognised that they are effective in killing myeloma cells. It has also been found that, when steroids are used with chemotherapy, the result is a greater response to treatment than when chemotherapy is used alone. 5 Steroids can also be used to treat relapsing myeloma, and as a form of maintenance treatment to sustain response to treatments. Steroids are usually given in tablet form, or intravenously (into a vein). Tablets should be taken with food or milk to help protect the lining of the stomach from irritation. 13 High dose chemotherapy (HDT) and stem cell transplantation Autologous stem cell transplantation (ASCT) involves giving initial treatment called induction treatment to remove the bulk of the myeloma. This is followed by the collection of the patients own healthy stem cells (hence the term autologous) before a high dose of chemotherapy, usually melphalan, is given with the aim of killing the remaining myeloma cells. The healthy stem cells are then returned to their blood, where they home in on the bone marrow and start to make new blood cells, through a process known as engraftment. A successful engraftment effectively rescues the bone marrow, enabling it to recover and re-establish blood cell production. HDT and ASCT following induction treatment therefore has the ability to kill more myeloma cells than would be possible with chemotherapy alone. This increases the likelihood of a longer remission and a better quality of life. However, HDT and ASCT is an intensive treatment option that is not suitable for everyone. It is generally limited to younger and/or fitter patients. 12 3
4 Thalidomide Thalidomide has had a relatively long history in the treatment of patients at all stages of myeloma in the UK. It is licensed for use for newly diagnosed patients who are not suitable for a stem cell transplant and who are over 65 years of age. Thalidomide has been shown to have several mechanisms of action that may affect myeloma cell survival. 14 By one route, thalidomide acts as an angiogenesis inhibitor, stopping tumours making their own blood vessels. 15 Typical side-effects include a heightened risk of infection due to lowered white blood cell count, tiredness and breathlessness due to drop in red blood cell count (anaemia) and an increased susceptibility to bruising due to decreased platelet levels in the blood. Examples of other side effects include; skin changes, nerve damage, dizziness, constipation, loss of fertility and blood clots. 13 Patients prescribed thalidomide should be regularly monitored. Thalidomide can cause the formation of a blood clot (or venous thrombosis) in certain veins of the body. This condition most often occurs in the legs, and is known as deep vein thrombosis. 14 Other Treatments Research is going on to help find more effective and less toxic treatments for myeloma. Treatments such as bortezomib (Velcade ) and lenalidomide (Revlimid ) are now available and are being used. Bortezomib (Velcade R ) Bortezomib is the first medicine in the class of anti-cancer drugs known as proteasome inhibitors. Since its introduction, it has had a significant positive impact on the treatment of myeloma. Its multiple mechanisms of action have proven to be effective in targeting myeloma cells causing a rapid reduction in paraprotein levels. Bortezomib works by temporarily blocking the actions of proteasomes. Proteasomes are involved in the removal, breakdown and recycling of damaged proteins or those that are no longer needed by the cell. As a consequence of temporarily blocking the actions of proteasomes, these proteins build up and become toxic, confusing the cell, and so cause it to die. Dividing myeloma cells rely more heavily on proteasomes than normal healthy cells, which divide slowly. They are therefore much more sensitive to bortezomib. Although healthy cells are often affected by bortezomib, they are able to survive and recover quickly from the dose of bortezomib used to treat myeloma. Bortezomib is normally given intravenously (into the vein) 16 and is now licensed to also be given via a subcutaneous (under skin) injection. 17 Typical side effects include peripheral neuropathy, which can cause numbness, tingling, increased sensitivity and pain in the hands, feet, arms or legs. Whilst less common than with conventional chemotherapy, bortezomib can sometimes affect blood counts, leading to fatigue and anaemia due to reduced red blood cells, increased susceptibility to infection due to lower white cell counts 16 and also increased risk of bruising due to lower platelet levels in the blood. 18 Other side effects include gastrointestinal disturbances, fatigue, low blood pressure and skin rashes. 16 Patients should be regularly monitored whilst taking bortezomib. Lenalidomide (Revlimid R ) Lenalidomide is an immunomodulatory drug (IMiD). This means that it works by modifying a patient s immune system. The main function of the immune system is to fight disease and infection. Lenalidomide has been shown to have many mechanisms of action that may affect myeloma cell survival. Lenalidomide is chemically similar to thalidomide which is also an IMiD used frequently to treat myeloma. Despite this similarity, however, lenalidomide does not appear to cause the same degree of side-effects as thalidomide, which means that patients generally find it easier to tolerate. Lenalidomide is given orally as a capsule, usually for 21 days followed by seven days rest. This constitutes one 28-day cycle and treatment is normally continued until the myeloma progresses again. Lenalidomide can be effective in controlling myeloma when it is given as a continuous, uninterrupted treatment. 19 Typical adverse events include an increased risk of infection due to a drop in level of white blood cells, fatigue due to a drop in the level of red blood cells (anaemia) 19 and increased risk of bruising due to drop in the level of platelets in the blood. 20 Other side effects include peripheral neuropathy leading to increased sensitivity, tingling and pain, constipation, tiredness and rash. 19 Patients should be regularly monitored whilst on treatment. Patient Care Further information about guidelines on patient care in myeloma can be found at 4
5 Further Information on Myeloma Myeloma UK The UK Myeloma Forum Leukaemia CARE Leukaemia and Lymphoma Research Cancer Research UK Macmillan Cancer Support References 1 Myeloma UK What is Myeloma? Available at: 2 Myeloma UK What causes Myeloma? Available at: 3 Cancer Research UK Myeloma risks and causes. Available at 4 Myeloma UK How long will I live? Available at: Last accessed at Myeloma UK Myeloma: Essential Guide. Available at: 6 Cancer Research UK Outlook & Stats. Available at: 7 Cancer Research UK The Stages of Myeloma. Available at: 8 CRUK How Chemotherapy works. Available at: Last accessed Myeloma UK. Response to treatment. Available at: Last accessed Myeloma UK Chemotherapy Infoguide. Available at: 11 BCSH and UKMF Guidelines on the management and diagnosis of Multiple Myeloma September Available at Last accessed Myeloma UK High Dose Therapy Infoguide. Available at: 13 Myeloma UK Steroid Info sheet. Available at: 14 Myeloma UK Thalidomide and Myeloma Infoguide. Available at: 15 Cancer Research UK Thalidomide. Available at: 16 Myeloma UK Velcade Infoguide. Available at: 17 Velcade Summary of Product Characteristics available at: 18 Cancer Research UK Bortezomib. Available at: 19 Myeloma UK Revlimid Infoguide. Available at: 20 Cancer Research UK Lenalidomide. Available at: 5
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