Blood cancer - myeloma

This section provides information about myeloma. This includes its causes, risk factors, symptoms, how it is diagnosed and the different types of myeloma treatments available.

About myeloma blood cancer

Myeloma (also called multiple myeloma), is a cancer of the plasma cells in your bone marrow. The bone marrow is where blood cells are produced. It's the 'spongy' material found in the centre of the larger bones in the body.

Plasma cells are a type of white blood cell that form part of your immune system. While normal plasma cells produce antibodies to help fight infection, with myeloma, these plasma cells become abnormal, and start to multiply in an uncontrolled way.

What happens when the cells become abnormal is they release a single type of antibody - known as paraprotein, M protein or immunoglobulin - with no useful function. And it's often by measuring the level of this paraprotein that myeloma is diagnosed and monitored.

Myeloma is not like other cancers. It doesn't show as a lump or tumour, for example. And most of the problems related to myeloma are caused by a build-up of the abnormal plasma cells and paraprotein in the blood or urine.

Myeloma is also called multiple myeloma, this is because it can affect different (multiple) parts of the body, wherever bone marrow is found - in the bones of the spine, skull, pelvis, rib cage, long bones of the arms and legs and areas around the shoulders and hips.

Myeloma is called a relapsing-remitting cancer. Put simply, this means that its symptoms can come and go. So sometimes the myeloma will cause symptoms that need to be treated, which can be followed by inactive periods (called a remission or plateau) where the myeloma doesn't cause any symptoms and so doesn't need treatment.¹

Myeloma facts

• Around 4,700 people are diagnosed with myeloma each year in the UK
• It's the second most common bone marrow cancer, yet it only accounts for 1% of all cancers
• Myeloma survival rates are increasing at the fastest rate among all cancer types in the UK.²

¹ Myeloma UK, What is myeloma? https://www.myeloma.org.uk/information/what-is-myeloma/
² Myeloma UK, Facts and figures. https://www.myeloma.org.uk/information/facts-and-figures/

Types of myeloma blood cancer

There is one main type of myeloma, but in different people, the cancerous plasma cells produce different antibodies - called paraprotein or immunoglobulin (Ig).

In every case of myeloma, only one type of immunoglobulin is abnormally overproduced, but the type varies from patient to patient.

The type of blood cancer you have doesn't usually affect the myeloma treatment you're offered but it can determine how the disease makes you feel.

Five basic immunoglobulins have been identified, and these are labelled A, G, M, D and E. The most common myeloma type is called IgG, and the rarest is IgE.

Light chain myeloma (IgG)
About 20% of people with myeloma don't produce complete immunoglobulins. They only produce part of the immunoglobulin, and this is called light chain or Bence Jones myeloma.

These light chains are smaller than complete immunoglobulins and show up in the urine, not the blood.

Non secretory myeloma
In fewer than 2% of people with myeloma (2%), immunoglobulin doesn't show up in the blood or the urine, so it's harder to diagnose this type of myeloma, called non secretory myeloma.

However, a new blood test called a serum free light chain test can help to detect small amounts of free light chain immunoglobulins in the blood - which is useful for diagnosing and monitoring non secretory myeloma.

Rare conditions related to myeloma
There are three other conditions of the plasma cells that are related to myeloma:

Monoclonal gammopathy of undetermined significance (MGUS)
MGUS is where plasma cells produce too many large protein molecules (immunoglobulins or paraproteins) that show up in the blood.

Though MGUS doesn't appear to do any harm or cause problems, it does not need treating. However, some people with MGUS may develop myeloma, and recent studies show that almost everyone who has myeloma already has MGUS.

Plasmacytoma
This is a tumour made up of plasma cells that are of all one type, and can be found in the bone or soft tissue. Over half of the people with plasmacytoma will go on to develop myeloma at some stage of their life.

Amyloidosis

Amyloidosis is a collection of conditions, where an abnormal protein called amyloid is produced by the plasma cells and collects in organs like the kidney or heart.

About 10 to 15% of people with myeloma either have, or develop, amyloidosis. But it is rare for people with amyloidosis to then go on to develop myeloma. Amyloidosis is often treated with chemotherapy, using the same drugs used for myeloma.

Causes and risk factors

The exact cause of myeloma isn't understood, but a few factors can increase people's risk of getting a disease:

Age, ethnicity and sex
The risk of myeloma seems to increase as we get older. It's very rare for people under 40 to have myeloma. And myeloma is almost twice as common in black populations as it is in white and Asian populations. It is also more common in men than in women.

Monoclonal gammopathy of undetermined significance (MGUS)
Studies show that almost everyone who has myeloma already has a rare medical condition called monoclonal gammopathy of unknown significance (MGUS).

MGUS is where there are too many immunoglobulins (a type of large protein molecule) in the blood, and is often detected by chance through routine blood tests. Thought it doesn't cause any symptoms, and does not generally affect your health or need treatment, some people with MGUS go on to develop myeloma.

Family history
Studies show that some people with a direct relative (a parent or sibling) with myeloma or MGUS are two or three times as likely to develop myeloma or MGUS, compared to people with no direct relatives with these diseases.

Lowered immunity
People who take medicines that may lower their immunity after an organ transplant may have three times the risk of myeloma, compared to the general population.

HIV infection or AIDS
Being infected with HIV (human immunodeficiency virus) or having AIDS (acquired immune deficiency syndrome) puts people at increased risk of developing myleoma.

Body weight
Much evidence shows that people who are overweight may have a slightly increased risk of myeloma compared to people with a healthy body weight.

It has to be noted that these risk factors account for a small proportion of cases of myeloma. And there is nothing to suggest that anything you do can cause you to develop myeloma. So even if you have one or more of these risk factors, it does not mean you will get myeloma.

Myeloma blood cancer symptoms and diagnosis

The most common symptom of myeloma is pain in the bones of the lower back or ribs.

About 70% of people diagnosed with myeloma initially complain of a lower back pain, or a pain in their ribs. This is happening because too many of the abnormal plasma cells are affecting the bone marrow, which may damage the bone - and other bones may be affected too, like the skull or pelvis.

Some other symptoms may include:

• tiredness and fatigue because of the lack of red blood cells (also called anaemia)
• kidney problems, caused by the paraproteins which are being overproduced by the myeloma cells - this can also cause tiredness and anaemia
• repeated infections, in particular the chest, caused by the shortage of normal antibodies
• loss of appetite, feeling sick, constipation, depression and drowsiness, which can all be caused by too much calcium in the blood (hypercalcaemia)
• unexplained bruising or bleeding, for example, nosebleeds or bleeding gums, this may happen because of a reduced number of blood platelets
• an unexplained loss of weight.

Most people who notice these symptoms are unlikely to have myeloma, as they are exactly like the symptoms of many more common and less serious illnesses too.

But you should always get any new or unusual symptoms looked into properly by a GP so you can treat any problems early.

Diagnosing myeloma
If you go to your GP to talk about your symptoms, they will ask questions about your health and carry out a simple physical examination.

If your doctor thinks you need further tests, they will arrange blood tests or x-rays that may be necessary at hospital.

Various types of blood tests are the main way to diagnose and monitor myeloma, and may include the following:

Serum protein electrophoresis
This is the main blood test used to diagnose myeloma. It measures the amount of abnormal antibodies (paraproteins) in the blood. This test is also used as a guide to see how well treatment is working.

Full blood count
This measures the levels of white blood cells, red blood cells and platelets in the blood. If any of the levels are low, this can show your doctor how your bone marrow has been affected by myeloma.

Urea and electrolytes (U&E) test
This blood test gives information on how well your kidneys are working.

Calcium level
This test measures the calcium levels in the blood, which are sometimes raised in myeloma.

Beta-2 microglobulin level
This measures the level of a protein produced by myeloma cells, and can help to show the activity level of a myeloma.

Albumin level
This test measures the level of a blood protein called albumin, which can indicate an advanced myeloma.

Serum free light chain assays
This is a type of test use to detect light chains in the blood and can help to diagnose and monitor light chain myeloma. Samples of your urine (pee) might also be taken to test for the Bence Jones protein.

At hospital you will see a consultant specialist called a haematologist, who specialises in conditions of the blood. They will ask about your general health and any previous medical problems.

The consultant will then examine you and arrange a series of tests that may include blood and urine tests, bone marrow biopsies and X-rays of your bones.

Bone marrow biopsies
If paraproteins show in your blood or urine, it's likely your doctor will want to take a sample of your bone marrow tissue (called a biopsy).

A bone marrow biopsy is usually taken from your hipbone (pelvis) or sometimes the breast bone. This biopsy will be performed. You'll be given a local anaesthetic to numb the area, then the consultant haematologist will gently pass a needle through your skin into the bone, to take a small sample of liquid marrow. This sample is then examined under a microscope (called a bone marrow aspiration) to see if it contains any myeloma cells.

The doctor will then take a small core of marrow from the bone (called a trephine biopsy), a procedure that takes a few minutes longer. A special type of needle - which is thicker than the needle used to take some bone marrow fluid - is passed into the bone marrow to take a small core of bone marrow.

After your bone marrow biopsy, you may feel a little bruised and ache for a few days, but this can be relieved with painkillers.

Cytogenetic and FISH tests on your biopsy
Every cell in the body contains chromosomes, which are made up of genes - these control all the cell's activities. In myeloma, there can be changes to chromosome structures in the myeloma cells, but not in the normal cells of the body.

Cytogenetic tests on the bone marrow samples from your biopsy will look closely for changes in the chromosomes. These tests may help to decide on the best treatment and predict how well the myeloma may respond to that treatment.

Another test called fluorescence in situ hybridisation (FISH) may also be used to see if there are specific changes to the myeloma cell chromosomes.

X-rays and scans
X-rays may be taken to check for any damage to the bones from the myeloma cells (lytic lesions). You'll usually have X-rays taken of your whole body, known as a skeletal survey, which can take up to an hour.

Stages of myeloma

Staging simply means describing the how far the cancer has spread. Knowing the stage of your blood cancer will help your consultant to plan the most effective myeloma treatment for you.

Unusually, myeloma is divided into three stages. Each stage indicates the effect that the disease is having on the body and how quickly or slowly the myeloma may develop.

This three-stage system is called the International Staging System (ISS), and refers to the levels of the blood proteins beta-2 microglobulin and albumin.

• Stage 1: This is called as early-stage myeloma, where the beta-2 microglobulin blood level is less than 3.5 milligrams for each deciliter (3.5mg/dL) and the albumin level is greater than or equal to 3.5g/dL
• Stage 2: This is classed as intermediate-stage myeloma, and is neither stage 1 or 3
• Stage 3: This is classed as advanced myeloma, where the beta-2 microglobulin level in the blood is greater than or equal to 5.5 mg/dL.

Myeloma treatment

Myeloma is rarely curable, but it is treatable. What is more, treatment can be highly effective at controlling the symptoms and helping to stop the disease from developing further.

At Circle Health, we use haemato-oncology to diagnose and treat all blood cancers, including myeloma. Treatment in most cases is chemotherapy, sometimes in combination with radiotherapy.

Benefits of haemato-oncology
Treatment for most people with myeloma helps to alleviates symptoms, improves survival and, for some people, can cure the disease.

Once our consultant haematologists know the stage of your myeloma, they can plan your treatment. The treatment type you will be offered depends upon a few factors, which includes your general health and the stage of your myeloma.

The aim of treatment
The aim of any treatment we provide is to get the myeloma under control, so it goes into remission - so that no abnormal myeloma cells can be found in the blood or bone marrow, and normal bone marrow starts to develop again.

However, a complete remission isn't always possible for everyone with myeloma. But treatment can still help to reduce the amount of myeloma in the body (called a partial response), or stop it from developing further.

Throughout your treatment, you will have tests to check for the amount of paraprotein and light chains in your blood and to see how the myeloma is responding to treatment.

Myeloma without symptoms
If the myeloma is diagnosed early and is developing slowly (sometimes called asymptomatic or smouldering myeloma), you might not need treatment immediately.

You'll see your consultant every few months and they will take blood samples to do tests - this is known as active monitoring. Treatment will only be started if the myeloma begins to develop quicker or if you experience symptoms (the myeloma is then sometimes called symptomatic or active myeloma).

Active myeloma
If your myeloma is active, the main treatments are chemotherapy, targeted therapies and steroids.

And, depending on your overall health and how the myeloma makes you feel, you might be offered a course of intensive chemotherapy (also called high dose) followed by a stem cell transplant.

But for people who would be able to tolerate the side effects of intensive chemotherapy treatment, there are options to have a combination of chemotherapy, targeted therapies and steroids.

Chemotherapy
You may have treatment with a single chemotherapy drug or a combination of different drugs. Steroids are usually given with chemotherapy to improve its effect.

Targeted therapies
This is another group of drugs commonly used to treat myeloma, and they might be used on their own or in combination with chemotherapy treatment. As with chemotherapy, steroids are often given with targeted therapy to improve its effect.

Bisphosphonates
Bisphosphonate drugs can also be given with chemotherapy. These help to prevent bone damage, relieve pain and may also help people to live longer.

Intensive chemotherapy with stem cell transplant
Also called high dose chemotherapy, this is an intensive chemotherapy drug treatment that can help to improve the chances of controlling your myeloma in the long term. It uses high doses of chemotherapy followed by a stem cell transplant.

Stem cell transplant
A stem cell transplant is where stem cells are injected into your vein through a drip to replace stem cells that the high dose chemotherapy has killed.

Stem cells are essential to our survival - they are embryonic blood cells in your bone marrow that develop into red blood cells, white blood cells and platelets.

Having a stem cell transplant enables you to tolerate higher doses of chemotherapy, to give the drugs more chance of curing the myeloma.

Maintenance therapy
If your myeloma goes into remission, then maintenance therapies may be used to keep the disease under control for longer - to suppress your symptoms.

But, for a few people, treatment doesn't help to control the effects of myeloma. In these cases, it's called refractory myeloma, and your consultant haematologist may offer you another type of treatment to help control the disease.

But for many people, treatment achieves a good response, yet the symptoms of myeloma often come back. This is sometimes called a relapsed myeloma - you will then be offered further treatment for this relapse.

Radiotherapy
Radiotherapy is often used to treat small areas of myeloma (sometimes called a localised disease) that are causing bone pain. This therapy is sometimes used in combination with high dose (intensive) chemotherapy treatments.

Surgery
Surgery is sometimes required to help repair or strengthen bones that have suffered damage by the myeloma.

Paying for your haemato-oncology treatment
Haemato-oncology costs are covered by most medical insurance policies, but please check with your insurer first. If you are paying for your own treatment the cost of the operation will be explained and confirmed in writing when you book the operation.

Ask the hospital for a quote beforehand, and ensure that this includes the consultants' fees and the hospital charge for your procedure.

Follow-up treatment
You'll have regular check-ups following your treatment. How often and for how long depends on the kind of treatment that you had.

At follow-up appointments, your consultant haematologist will ask how you're feeling and examine you. You might also need a blood test, CT scan, ultrasound, X-rays or a combination.

Want to know more?
If you'd like to read more about blood cancer, treatment or living with blood cancer, please visit cancerresearchuk.org.uk.