Myeloma

What is myeloma?

Myeloma is a cancer of certain white blood cells, called plasma cells. The cancerous plasma cells build up in the bone marrow. They also make a lot of one type of antibody. As a result, various symptoms develop. Myeloma is sometimes called multiple myeloma or myelomatosis.

What are the bone marrow, plasma cells and antibodies?

The bone marrow is the soft 'spongy' material in the centre of bones. The bone marrow is where blood cells are made by stem cells. Stem cells are the immature cells that can develop into mature blood cells. Stem cells constantly divide and produce new cells. Some new cells remain as stem cells, and others go through a series of maturing stages ('precursor' or 'blast' cells) before forming into mature blood cells. The blood cells made by stem cells are red blood cells, white blood cells and platelets.

You make millions of blood cells every day. There is normally a fine balance between the number of blood cells that you make, and the number that die and are broken down. Various factors help to maintain this balance. For example, certain hormones in the bloodstream and chemicals in the bone marrow called 'growth factors' help to regulate the number of blood cells that you make.

Plasma cells are one type of white blood cell. White blood cells are a main part of the immune system which defend the body from infection. There are various types of white blood cells including plasma cells.

Antibodies (immunoglobulins) are made by plasma cells. They are proteins that attach to, and help to destroy, germs such as bacteria and viruses. Normally, the plasma cells make a large number of different antibodies, each able to attack different bacteria and viruses.

What is cancer?

Cancer is a disease of the cells in the body. The body is made up from millions of tiny cells. There are many different types of cells in the body, and there are many different types of cancer which arise from different types of cell. What all types of cancer have in common is that the cancer cells are abnormal and do not respond to normal control mechanisms. Large numbers of cancer cells build up either because they multiply 'out of control', or they live much longer than normal cells would do, or both. Myeloma is one type of cancer.

What happens in myeloma?

As with other cancers, what seems to happen is that the cancer starts with one abnormal cell. In the case of myeloma, one plasma cell at first becomes cancerous. This abnormal cell then multiplies to produce many identical abnormal plasma cells (a 'clone' of cells). The cancerous plasma cells mainly collect in the bone marrow and continue to multiply without any control.

In the vast majority of cases of myeloma, the abnormal plasma cells make large quantities of one antibody. This single type of antibody is called a paraprotein (or sometimes called a monoclonal antibody, as it is an antibody which comes from a single clone of plasma cells).

There are several different types of antibody. (Antibodies are sometimes called immunoglobulins or Ig for short.) These are called IgM, IgG, IgA, IgD and IgE. Myelomas are sub-classified by the type of antibody that they make. For example, IgG myeloma is the most common type.

What causes myeloma?

It is not known why a plasma cell becomes cancerous. Factors such as infection, or chemicals, or other environmental factors may play a part in damaging cells and causing cancers such as myeloma. However, no factor has been proven as a cause for myeloma. It is not a hereditary disease.

How common is myeloma and who does it affect?

Myeloma is uncommon. It develops in about 4000 people in the UK each year.

Most cases occur in people over the age of 50, and it becomes more common with increasing age. The average age of diagnosis is 70. Rarely, it occurs in younger adults, and it does not occur in children. Men are affected more often than women.

What are the symptoms and problems with myeloma?

There may be no symptoms at first in the early stages of the disease. Some people are diagnosed by chance because they have a blood test done for other reasons which may detect early myeloma. As the disease progresses, symptoms develop.

The symptoms and problems which develop are mainly due to the uncontrolled production of plasma cells in the bone marrow, and the excess amount of antibody (paraprotein) that the plasma cells make.

Bone damage and related problems

The increasing numbers of plasma cells in the bone marrow act like growing tumours ('plasmacytomas') inside the bones. They also make a chemical that can damage bone. In time, small parts of bone are destroyed and are called 'lytic lesions'. The term 'multiple myeloma' is sometimes used which means there are multiple (lots of) areas in bones throughout the body which are affected.

The damage to bone can cause:

• Bone pain. This is often the first symptom and can become severe. Any bone can be affected but the most common sites where pain first develops are the lower back, pelvis, and the ribs. The pain tends to be persistent, and made worse by movement.
• Fractures. Affected bones may easily fracture (break) following a mild injury or even no injury.
• Compression of nerves coming out of the spinal cord. The compression usually happens because of fractures of the vertebrae (the bones surrounding the spinal cord). This can cause a variety of symptoms such as weakness in muscles of the legs, numbness of areas of the body or legs, bladder or bowel problems, and pain. If you have any of these symptoms you need to seek urgent medical attention.
• Hypercalcaemia. This means a high level of calcium in the blood (due to the bone breaking down). This can make you very thirsty and can cause nausea and vomiting, dehydration, constipation and also kidney damage.

Bone marrow failure

Much of the bone marrow fills with abnormal plasma cells. Because of this, it is difficult for normal cells in the bone marrow to survive and develop into normal mature blood cells. Therefore, problems which can develop include:

• Anaemia. This occurs as the number of red blood cells goes down. This can cause tiredness, breathlessness and other symptoms. You may also look pale.
• Blood clotting problems. This is due to low levels of platelets. This can cause easy bruising, bleeding from the gums, and other bleeding-related problems.
• Serious infections. The abnormal plasma cells only make one type of antibody. This does not protect against infection. There is a reduced number of normal plasma cells and other types of white blood cells which usually combat infection. Therefore, serious infections are more likely to develop.

Kidney damage

The kidneys may be damaged by an increased calcium level in the bloodstream, and/or by the high level of the abnormal antibody (paraprotein).

Hyperviscosity

This means that the blood may become too thick due to a very high level of paraprotein. Symptoms of hyperviscosity occur in less than one in ten cases of myeloma and include problems such as bruising, nose bleeds, hazy vision, headaches, sleepiness and various other symptoms. If you develop these symptoms then you need to seek medical advice without delay.

Amyloidosis

This is an uncommon complication of myeloma. This is a condition where abnormal protein (amyloid) accumulates in various parts of the body. It can cause various symptoms.

How is myeloma diagnosed?

Tests commonly done to confirm the diagnosis of myeloma include:

• A blood or urine test to detect the paraprotein.
• X-rays of bones. The areas of damaged bones often show up as typical patterns on X-ray pictures. MRI, CT or ultrasound scans may be done if X-ray tests do not give enough detailed information. (There are separate leaflets that give details of these tests.)
• A bone marrow sample. For this test a needle is inserted into the pelvis bone, or sometimes the breastbone (sternum). Local anaesthetic is used to numb the area. Then a small amount of marrow is removed. The sample is placed under the microscope to look for abnormal cells. The diagnosis is confirmed when a large number of plasma cells are seen in the bone marrow sample. (See separate leaflet called 'Biopsy - Bone Marrow ' for details.)

These tests may be repeated from time to time to monitor the progress of the disease and also to monitor the response to treatment.

Other tests which are commonly done to assess the severity of the disease and to monitor the response to treatment include:

• Blood tests to check on your kidney function.
• Blood tests to check the level of calcium in your blood.
• Blood tests to check the level of paraprotein in your blood.
• Chromosome and gene testing of the myeloma cells. This can help to identify the exact type of myeloma so that doctors can decide which treatment is best.
• Blood tests to measure proteins in the blood called beta-2 microglobulin and albumin. The levels of these proteins are affected by myeloma and give an indication as to the severity of the disease.

Other disorders related to myeloma

The following are other plasma cell abnormalities. If you are diagnosed with any of these conditions, myeloma may develop sometime later, but not always.

• Isolated (solitary) plasmacytoma of bone. In this condition only one plasma cell tumour is found in a bone. There is no other evidence of myeloma anywhere else in the body.
• Extramedullary plasmacytoma. In this condition, one or more plasma cell tumours occur outside the bone marrow. These most commonly occur in the tonsils or the tissues around the nose.
• Monoclonal gammopathy of unknown significance (MGUS). In this condition a paraprotein is found in the blood without other symptoms or signs of myeloma. (Monoclonal gammopathy is another way of saying a high level of a monoclonal, or single type of, antibody.) This condition does not require treatment but needs monitoring. Around 1 in 100 people with MGUS develop myeloma in the future.

What are the aims of the treatment for myeloma?

Treatments may be used to treat and control the myeloma itself. Also, to ease symptoms and complications of the myeloma. Treatments options are briefly discussed below.

However, different treatments suit different people. You should have a full discussion with a specialist who knows your case. They will be able to give the pros and cons, likely success rate, possible side-effects, and other details about the treatment options for myeloma.

Treatments to control the myeloma

In many cases, treatment can control the myeloma and put the disease into 'remission'. Remission is not necessarily a cure. Full remission means that tests cannot detect the abnormal plasma cells in the blood or bone marrow, and the bone marrow is producing normal blood cells again. Some remissions are 'partial' which means there is some improvement, often a great improvement, but some myeloma cells remain. In many cases where there is remission or partial remission, at some point in the future the disease returns (relapses). Further treatment may be considered if the disease relapses. However, in time, the relapses become more difficult to treat.

Treatments that may be used include one or more of the following:

Chemotherapy

Chemotherapy is a treatment which uses anti-cancer drugs to kill cancer (myeloma) cells, or to stop them from multiplying. Various drugs are used and myeloma may be treated with chemotherapy drugs given as tablets or injections. The exact combination of drugs used, and the length of the course of chemotherapy, depends on various factors. For example, the severity of the myeloma, the exact type of myeloma, if you have kidney damage, your age and general health. (See separate leaflet called 'Chemotherapy' for more details.)

If a course of chemotherapy achieves a remission, you may then be advised to take drugs as a regular 'maintenance' treatment. These may include interferon, steroids, thalidomide or bortezomib. This is in effect 'low level' chemotherapy which aims to keep you in remission for as long as possible.

Recent developments in drugs to combat myeloma have improved the outlook. For example, thalidomide and bortezomib are relatively new and seem to be improvements on previous drugs. Another new drug that shows promise is lenalidomide. Various research trials of these drugs, and combinations of drugs, are underway.

Stem cell transplant

A stem cell transplant may be an option. It is an intensive treatment that is not suitable in all cases. However, this treatment generally gives the best chance of a complete remission.

Stem cells are the immature cells that develop into mature blood cells in the bone marrow. Briefly, a stem cell transplant involves high dose treatment of chemotherapy (and sometimes radiotherapy) to kill all the abnormal plasma cells. However, this also kills the stem cells that make normal blood cells. So, after the high dose treatment, some stem cells are given to you via a drip into a vein (like having a blood transfusion). The stem cells are usually obtained from the blood of the patient with the myeloma before the high dose treatment is started. The stem cells from the transfusion make their way to the bone marrow where they then multiply and make normal blood cells, including plasma cells. (See separate leaflet called 'Stem Cell Transplant' for more details.)

Radiotherapy

Radiotherapy is a treatment which uses high energy beams of radiation which are focused on cancerous tissue. This kills cancer cells, or stops cancer cells from multiplying. For myeloma, radiotherapy is mainly used to treat severe localised problems and plasmacytomas. For example, to treat severe pain and/or pressure on nerves due to a damaged spinal bone because of a build up of myeloma cells in the bone. (See separate leaflet called 'Radiotherapy' for more details.)

Treatments to ease symptoms

Depending on the effects of the myeloma, one or more of the following may be advised:

• Painkillers - to ease any pain.
• A bisphosphonate drug. This reduces the bone destruction that occurs with myeloma and helps to lower a high calcium level.
• Erythropoietin. This is a hormone that helps to increase the number of red cells made in the bone marrow. It may be used to help improve anaemia.
• Blood transfusions to correct anaemia.
• Plasma exchange or exchange blood transfusions if you have a very high level of paraprotein in your blood which is causing hyperviscosity symptoms.
• Antibiotics if you develop infections.
• Surgery is sometimes needed to help heal fractured bones, or to ease pain from fractured bones, or to ease pressure on a trapped nerve due to fractures of the spinal bones.
• Kidney dialysis if you develop kidney damage and kidney failure.

People with myeloma will also usually be advised to drink plenty of fluids (at least three litres a day). This helps to lower a high calcium level.

What is the prognosis (outlook)?

In general, with treatment, about half of people with myeloma are alive and well 3-4 years after diagnosis. However, this is the general overview. In some cases the disease responds very well to treatment and survival is much longer. In particular, a successful stem cell transplant gives a good chance of a complete remission. In some cases the disease does not respond to treatment very well, or life-threatening complications develop such as kidney failure.

The treatment of cancer and myeloma is a developing area of medicine. New treatments continue to be developed and the information on outlook, above, is very general. As mentioned above, there are some newer drugs that have been introduced in the last few years that show promise to improve the outlook. The specialist who knows your case can give more accurate information about the outlook for your particular situation.

Further help and information

Myeloma UK

Broughton House, 31 Dunedin Street, Edinburgh EH7 4JG
Myeloma Infoline: 0800 980 3332 Tel: 0131 557 3332
Web: www.myeloma.org.uk
A charity which aims to assist those affected by myeloma and their families. They also produce a range of information about various aspects of myeloma and its treatment.

Macmillan Cancer Support

Tel: 0808 800 1234 Web: www.macmillan.org.uk
Provide information and support to anyone affected by cancer.

Cancer Research UK

Web: www.cancerhelp.org.uk provides facts about cancer including treatment choices.

Other support groups

See www.patient.co.uk/selfhelp.asp for a list of self help and support groups for cancer patients.