Multiple myeloma

Multiple myeloma, also known as myeloma, is a type of bone marrow cancer.

Introduction

Multiple myeloma, also known as myeloma, is a type of bone marrow cancer.

Bone marrow is the spongy tissue found at the centre of some bones. It produces the body's blood cells.

The cancer affects the plasma cells (a type of blood cell) inside the bone marrow, which are an important part of the immune system.

Myeloma does not usually take the form of a lump or tumour. Instead, the myeloma cells divide and expand within the bone marrow.

Myeloma often affects many places in the body where there is bone marrow, which is why it is called multiple myeloma. This includes the:

  • bones of the spine
  • skull
  • pelvis
  • rib cage
  • areas around the shoulders and hips, and sometimes
  • the legs and arms

In the early stages, myeloma may not cause any symptoms. It is often only suspected or diagnosed following a routine blood or urine test.

However, myeloma will eventually cause a wide range of symptoms including tiredness, infections, bone pain and bone fractures.

Read more about the symptoms of multiple myeloma.

What causes multiple myeloma?

It is not known what causes the plasma cells inside the bone marrow to become cancerous.

However, research has suggested that there are a number of factors that may increase your chance of developing multiple myeloma. These include:

  • having a family history of myeloma
  • having a lowered immunity due to taking immunosuppressants, or having a condition such as HIV or AIDS
  • being overweight or obese

Read more about the risk factors for multiple myeloma.

When to see your doctor

You should always see your doctor if you have any of the following symptoms:

  • unexplained tiredness that lasts for more than two weeks
  • persistent unexplained bone pain, particularly in your ribs or lower back
  • unexplained weight loss
  • passing lots of urine and always feeling thirsty
  • weakness, numbness or tingling in your arms or legs
  • loss of bladder or bowel control (urinary incontinence and bowel incontinence)

Although these symptoms are not usually the result of multiple myeloma, they still need to be investigated by your doctor.

Your doctor will examine you to check for bone tenderness, bleeding, signs of infection, and any other symptoms that suggest you may have myeloma.

Blood tests play an important part in diagnosing myeloma. They can be used to check whether your bone marrow (which makes your blood) is functioning properly and whether your blood contains the abnormal proteins produced by myeloma cells.

A urine test will also be needed to help determine whether there is any underlying damage to your kidneys or myeloma protein in your urine.

If your doctor thinks that you may have myeloma, they will refer you to a consultant haematologist (a specialist in blood conditions) for further tests.

Read more about how multiple myeloma is diagnosed.

Treating multiple myeloma

For most people with multiple myeloma there is no cure, but treatment can control the progression of the cancer for several years or, in some cases, many years (see below).

The three main goals of treatment are to:

  • bring the myeloma under control using various combinations of anti-myeloma treatments that remove the cancerous cells from your bone marrow
  • treat the symptoms associated with myeloma, such as anaemia and bone pain
  • reduce the risk of developing fractures and bone disease using medication to protect the bones

Read more about treating muliple myeloma.

Outlook

As with other types of cancer, the outlook for someone with multiple myeloma will depend on the stage the condition is at when they are diagnosed.

Age and fitness are also important factors, as well as the type of treatment you have. There are some very intensive treatments for myeloma, but to have them you often need to be otherwise fit and healthy.

Symptoms

In the early stages, multiple myeloma may not cause any symptoms or complications, and may only be diagnosed after a routine blood or urine test.

However, it will eventually cause a wide range of symptoms and complications. The most common symptoms are outlined below.

Bone pain

Pain can be a symptom of the bone disease that often occurs in myeloma. The middle or lower back, rib cage and hips are most frequently affected. The pain is often persistent and described as dull and aching, and it is often made worse by movement.

Bone fractures

The spine and ribs are the bones that most commonly fracture as a result of myeloma bone disease.

Breaks can occur with only minor or no pressure or injury. Fractures of the spine (vertebrae) can cause the sections of the spine to collapse or 'crush', leading to height loss, pain and occasionally compression of the spinal cord (the main column of nerves running down the back).

Compression of the spinal cord can cause pins and needles, numbness and weakness in the legs and feet, and sometimes problems going to the toilet. These symptoms require urgent medical attention.

Tiredness

Patients with myeloma often have persistent, overwhelming tiredness. This may be due to the myeloma itself or its complications. The side effects of treatment can also make the tiredness worse.

Effects on the bone marrow

Anaemia

Anaemia is a lack of red blood cells. It can occur as a result of the myeloma itself, or as a side effect of treatment. If you have anaemia, you may feel very tired and breathless.

Lowered immunity

People with myeloma are particularly vulnerable to infection. This is because the condition interferes with the immune system (the body's natural defence against infection and illness), making you more susceptible to infection.

Low platelets (blood clotting cells)

[Bruising] and bleeding can often occur in myeloma because the plasma cells (myeloma cancer cells) in your bone marrow stop platelets from being made.

Hypercalcaemia

Hypercalcaemia is where the level of calcium in the blood is too high. It can develop in people with myeloma because bone disease causes too much calcium to be released from affected bones.

Kidney damage

Kidney damage can occur in people with myeloma for a variety of reasons.

The abnormal protein produced by myeloma cells can damage the kidneys, as can other complications, such as hypercalcaemia and dehydration. Also, some medications that are used to treat myeloma can occasionally cause kidney damage.

Causes

In multiple myeloma, it's not known what causes the plasma cells inside the bone marrow to become cancerous.

However, research has shown that some people who develop multiple myeloma have previosly had a rare condition called monoclonal gammopathy of unknown significance (MGUS).

MGUS

A person with MGUS has an excess number of protein molecules called immunoglobulins in their blood. The condition does not cause any symptoms and treatment is not required.

Some people with MGUS later develop myeloma, so if the results of routine blood tests show that you have MGUS, you will be referred to a specialist for regular check-ups.

Family history

Research has also shown that if you have a close relative (a parent, brother, sister or child) with myeloma or MGUS, you are 2-3 times more likely to develop myeloma or MGUS compared to someone with no family history of these conditions.

Lowered immunity

If you take medicines that lower your immunity, your risk of developing myeloma is thought to increase by up to three times compared to someone who does not take immunity-lowering medication.

Your risk of getting myeloma is also increased if you have a condition that lowers your immunity, such as HIV or AIDs.

Weight and diet

If you are overweight or obese, you may have a slightly increased risk of developing myeloma compared to someone with a healthy weight.

However, diet does not appear to have any bearing on myeloma risk, although the evidence in this area is limited.

Exposure to chemicals

Some studies have suggested that people who work in certain occupations may have an increased risk of developing myeloma as a result of being exposed to certain chemicals.

The occupations identified as possibly having an increased risk are:

  • the petrol or oil industry
  • farming
  • wood working
  • the leather industry
  • painting and decorating
  • hairdressing
  • rubber manufacturing
  • fire-fighting

However, the research in this area is limited and there is insufficient evidence to show that these occupations carry an increased risk of myeloma.

Radiation exposure

Studies have also suggested that people who are exposed to high levels of radiation may have an increased risk of developing myeloma (as is the case with other types of cancer).

Medicines

Small-scale studies have suggested that using paracetamol, insulin, or medicines used to treat gout (a condition where sodium urate crystals form inside joints) may increase your myeloma risk.

Diagnosis

Multiple myeloma is a rare type of cancer that initially has few or no symptoms. This means that a diagnosis can often be delayed.

Your doctor will examine you and ask about your symptoms, medical history and overall health.

During the examination, your doctor will look for things such as bleeding, signs of infection and specific areas of bone tenderness.

They may ask you to have blood tests and a urine test (see below) to check for the presence of certain types of antibodies (proteins).

After looking at your blood test results, if your doctor suspects multiple myeloma, they will refer you to a haematologist (medical doctor who specialises in conditions that affect the blood).

The haematologist will carry out further blood and urine tests, scans, X-rays and a bone marrow test.

Blood tests

A number of blood tests are used to help diagnose multiple myeloma.

An erythrocyte sedimentation rate (ESR) test, or plasma viscosity (PV) test, is a type of blood test that shows whether there are unusually high levels of proteins in your blood that make it more viscous (thick). If you have myeloma, your ESR or PV will usually be raised.

You will also have blood tests to measure the type and number of abnormal antibodies produced by the cancerous plasma cells. The test can be used to help both diagnose and manage myeloma.

You will also have a full blood count (FBC) to check your levels of the different types of blood cells. In particular, your doctor will be looking for a low number of red blood cells and platelets (tiny cell fragments that cause the blood to clot).

Other blood tests may also be used to check the functioning of your liver and kidneys. Your blood calcium level may also be checked. In myeloma, the calcium level can be high. Many of these tests will be repeated on more than one occasion.

Urine tests

A urine sample will be checked for the abnormal proteins produced by the cancerous plasma cells. The abnormal proteins are known as ‘monoclonal light chains’ and are sometimes referred to as bence jones protein.

These proteins can damage your kidneys as they pass through them from the blood to the urine. You may be asked to collect all of the urine you pass over a 24-hour period. This sample can be used to check the quantity of proteins being produced and how well your kidneys are functioning.

X-rays and other scans

Large quantities of plasma cells produced in your bone marrow can damage the hard outer layer of your bones. You should tell your specialist if you have bone pain in certain parts of your body.

You will have X-rays taken of your long bones, skull, spine and pelvis to help identify any damage. You may also have a chest X-ray.

Other scans, such as computerised tomography (CT) scans and magnetic resonance imaging (MRI) scans may also be carried out.

Bone marrow test

A bone marrow test is usually used to confirm a diagnosis of multiple myeloma.

A needle will be used to take a small sample of bone marrow (biopsy) from one of your bones, usually the pelvis. A sample of bone may also be removed. The biopsy will be carried out using a local anaesthetic.

The sample of bone marrow (and bone) will be examined in a laboratory to check for the presence of cancerous plasma cells.

Treatment

If you have multiple myeloma, you will be cared for by a team of healthcare professionals usually led by a consultant haematologist who specialises in myeloma.

The team will discuss your condition and recommend what they think is the best treatment for you. However, the final decision will be yours.

Before visiting hospital to discuss your treatment options, it may be useful to write a list of questions that you would like to ask the specialist. For example, you may want to find out the advantages and disadvantages of a particular treatment.

There are two main aims in treating multiple myeloma. These are to:

  • bring the myeloma under control using various combinations of anti-myeloma treatments that remove the cancerous cells from your bone marrow
  • treat the symptoms associated with myeloma, such as anaemia and bone pain

Bringing myeloma under control

Not everyone diagnosed with myeloma will need immediate treatment if the condition is not causing any problems. This is sometimes referred to as asymptomatic or ‘smouldering myeloma’.

If you do not need treatment, you will be actively monitored for signs that the cancer is beginning to cause problems. If you do need treatment, the options outlined below are most commonly used.

It is important to understand that although myeloma is treatable, for most people it is not currently curable. This means that additional treatment is always required when the cancer comes back. The most commonly used treatments for when myeloma reoccurs are also described below.

Initial treatment for myeloma may either be:

  • non-intensive - for older or less fit patients
  • intensive - for younger or fitter patients

There is no particular age cut-off for who can have intensive treatment and who can have less-intensive treatment, and this is usually a decision based on the biological age (or fitness) of the individual.

However, as a general rule, people younger than 65 are more likely to be candidates for intensive therapy. For those over 70, non-intensive treatment is more likely to be recommended. Those aged in between will be given careful consideration as to what treatment group they fall into.

Both treatment intensities are very effective, but intensive treatment is thought to be too toxic for older or less fit patients.

All patients who require treatment will almost certainly aim to start with a combination of three anti-myeloma medicines.

These medicines all have different ways of working and work very effectively together at killing myeloma cells (much more effectively than if they were given on their own).

In the younger and/or fitter group of patients, this is called induction treatment because it is almost always followed by additional treatment known as high-dose therapy and stem cell transplantation (see below).

In the older and/or less fit group, this treatment is referred to as initial or frontline treatment. It is almost always identical to the induction treatment given in the younger/fitter group, but some of the medicines may be given in modified doses or timings.

These treatment combinations usually consist of three medicines, including a chemotherapy medicine (either melphalanor cyclophosphamide), a steroid medicine (examethasone or prednisolone and either thalidomide or velcade).

Together with your consultant haematologist, your team will decide the most appropriate combination that best suits your myeloma and personal preferences. The medicines are described in more detail below.

Steroids

Steroid medication is similar to a type of hormone found naturally in the body. Dexamethasone and prednisolone are steroids often used to treat myeloma. The steroids work by killing the cancerous plasma cells that develop in the bone marrow.

Steroids are taken by mouth (orally) and are best taken at breakfast with food. Possible side effects include heartburn, indigestion, mood changes and problems falling asleep.

Thalidomide

Thalidomide is a medication that was introduced in the 1950s to treat morning sickness, but it was later found to cause birth defects. However, research has shown that thalidomide can be effective in killing myeloma cells.

Thalidomide tablets are usually taken during the evening with food. Due to the risk of causing birth defects, it is important to use reliable contraception, such as a condom, while taking thalidomide.

It is likely you will have to sign a confirmation form stating you are aware of the risks of birth defects and of the precautions you need to take.

Common possible side effects of thalidomide include:

  • sleepiness
  • constipation
  • loss of appetite
  • headaches
  • skin rashes
  • numbness or tingling in the hands and feet

There is also a risk you may develop a blood clot when taking thalidomide. Therefore, you may be given aspirin or low molecular weight heparin to help prevent blood clots.

Contact a member of your cancer team immediately if you develop pain or swelling in one of your calves, or if you have chest pain and/or breathlessness.

Chemotherapy

[Chemotherapy] and [cyclophosphamide]. These two medicines work in a similar way and are sometimes used interchangeably.

These treatments are mostly given by mouth. They are reasonably well tolerated and side effects are mild. Possible common side effects include:

  • infection (se below)
  • nausea
  • vomiting
  • hair loss
  • tummy upsets

Your clinician will give you specific dietary advice and information about your risk of developing potentially serious infections.

Bortezomib

Bortezomib belongs to a relatively new class of anti-cancer medicines called proteasome inhibitors. It is particularly effective against myeloma cells.

All cells have an internal recycling protein known as the proteasome. Cells depend on this to recycle the things they need to grow and to dispose of the things that may be harmful to their survival.

Bortezomib blocks the functioning of proteasome, causing the myeloma cell to die.

Possible side effects of bortezomib include:

  • tiredness
  • nausea
  • diarrhoea
  • numbness or tingling in your hands and feet

There are some limitations as to which newly diagnosed patients should get bortezomib, but your doctor and/or nurse will discuss this with you.

Your doctor or nurse will tell you about your treatment and possible side effects to look out for. As with all treatments, it is important to let your doctor or nurse know of any side effects immediately.

Intensive treatment

Intensive treatment involves giving a much higher dose of chemotherapy in an attempt to destroy a larger number of myeloma cells, resulting in a longer period of remission (where there is no sign of active disease in your body).

However, as this treatment approach also knocks down healthy bone marrow, stem cells are transplanted to rescue the bone marrow. This treatment is known as high-dose therapy and stem cell rescue or transplantation.

In most cases, stem cells will be collected from the patient before they have the treatment (autologous transplantation). In rare cases, the cells are collected from a sibling (brother or sister) or an unrelated donor (sibling or match unrelated donor transplantation). An unrelated transplant is usually only performed after an autologous transplant.

Intensive treatment is associated with significant side effects and requires a 2-3 week stay in hospital and a 3-6 month recovery period, or an autologous transplant.

A transplant from another person can be much more complex so is not usually a treatment option for older people or those with a poor level of fitness.

Read more about stem cell transplants.

Maintenance treatment

Maintenance treatment is occasionally given to prolong treatment benefits. However, further research is underway to establish its role in the treatment of myeloma, which patients require maintenance, and who are most likely to benefit.

Treating the symptoms and complications of myeloma

Radiotherapy

Radiotherapy can be used to help relieve bone pain. It involves directing high-energy waves of radiation at bones weakened and damaged by cancerous cells.

The radiation reduces the number of cancerous cells in the bone, giving the bone a chance to repair itself. You should only need 1-2 sessions of radiotherapy to reduce the pain. However, longer courses are often used if there is compression of the spinal cord.

Read more about the latest (2011) guidelines for radiotherapy treatment for multiple myeloma (PDF, 346KB).

The side effects of radiotherapy usually pass after the course of radiotherapy has been completed. Depending on the dose given and the site treated, side effects can include nausea, sickness, skin rashes, pain and tiredness.

Bisphosphonates

Bisphosphonate medication can be used to help prevent bone damage and reduce the levels of calcium in your blood.

Bone usually goes through a continuous cycle of repair, where the body replaces old bone cells with new ones.

In myeloma, cancerous plasma cells disrupt this process, causing the bones to weaken. Bisphosphonates help to stop this happening and reduce both fractures and pain. Recent evidence suggests they may also have effects on survival.

Read more about the Medical Research Council’s Myeloma IX trial: the impact on treatment paradigms.

Bisphosphonates are either given as tablets or by injection. The most common side effects include stomach pain, nausea, vomiting and diarrhoea. You should speak to your cancer team if you are finding any of these side effects troublesome.

Treatments for anaemia

If you have anaemia as a result of having a low number of red blood cells, blood transfusions can be used to increase your red blood cell count.

In certain situations, you may also be given a medication called erythropoietin to encourage production of new red blood cells.

Surgery

In some cases, surgery may be needed to repair or strengthen damaged bones. Compression fractures of the spine may be treated using two fairly new surgical techniques known as:

  • percutaneous vertebroplasty - wherea special type of quick-drying cement is injected into the affected bone to strengthen it and reduce the risk of fracture
  • balloon kyphoplasty - wherea tiny balloon is inserted into the affected vertebra (bone of the spine), inflated and removed, and then the space is filled with a special type of cement

The National Osteoporosis Society provides more information about percutaneous vertebroplasty and balloon kyphoplasty (PDF, 175kb).

Relapse treatment

When the myeloma returns, you will be given an additional course of a combination of anti-myeloma treatments. This usually involves two or three medicines to try to control the myeloma again.

Treatment for relapsing myeloma is based on the same principles as those used for treating newly diagnosed myeloma and the treatment itself is also similar.

However, high-dose therapy and stem cell transplantation in younger and/or fitter patients is less commonly used, but is increasingly being considered as an option in patients who have had a sustained response to a first autologous transplant. Therefore, most patients, regardless of age and fitness, are treated similarly.

All the medicines described above are used in various combinations to treat relapsed myeloma. However, the important points below are worth noting.

  • Bortezomib is only approved for your first relapse, and patients must achieve a certain response to be able to continue treatment. Your doctor and/or nurse will explain this to you.
  • A medicine called lenalidomide (Revlimid) has recently been approved for treating adult multiple myeloma patients who have received at least one prior therapy (see below).

Lenalidomide

Lenalidomide works in a similar way to thalidomide in that it blocks the blood supply to the cancerous cells, and also helps the immune system fight the myeloma.

However, as lenalidomide can reduce the number of white blood cells in your blood, you will be more vulnerable to infection.

You should let your care team know if you think you may have an infection - for example, if you have a high temperature or if you feel unwell.

Lenalidomide also reduces the number of platelets in your blood, which means your skin can be easily bruised and you can bleed easily. Again, you should report these symptoms to a member of your care team.

If you are taking lenalidomide there is risk of developing a blood clot. Contact a member of your cancer team immediately if you develop pain or swelling in one of your calves, or if you have chest pain and/or breathlessness.

Read more about the European Medicines Agency’s 2013 approval of lenalidomide for treating patients with multiple myeloma.

Clinical trials

Cancer treatments have improved considerably over the past few decades. Some of these improvements have been due to patients taking part in clinical trials. Myeloma is a good example of this. Therefore, you may be asked to take part in a clinical trial.

Clinical trials usually involve comparing a new treatment with an existing treatment to see whether the new treatment is more or less effective.

It is important to remember that if you are given a new treatment there is no guarantee it will be more effective than an existing treatment.

There will also never be any pressure for you to take part in a trial if you do not want to.

[Search clinical trials for multiple myeloma].

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