Treating myeloma

When first diagnosed people with myeloma will be given initial treatment, this can be generally categorised into two groups:

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

There is no particular age cut-off for who can have intensive treatment and who can have less-intensive treatment; 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 inbetween 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.

In the younger, 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 intensive treatment).

In the older, or less fit, group this treatment is referred to as initial or frontline treatment.

In general the treatment of myeloma can be thought of in three different groups. These are:

1. Anti-myeloma treatments
2. Supportive care treatments
3. Active monitoring.

On completion of the tests described above, your doctor should have a clear and comprehensive picture of the specific characteristics of your myeloma. The presence of complications, caused by the myeloma damaging specific organs and tissues of the body, can also help to determine the characteristics of your myeloma. These are usually referred to by the acronym ‘CRAB’ which describes the four main complications that are generally observed in myeloma:

C-calcium elevation

R-renal (kidney) impairment

A-anaemia

B-bone damage (lytic lesions)

Results from the tests and investigations listed above, together with CRAB, will help decide when treatment should begin, what that treatment should be, and provide a baseline against which response to treatment and disease progression can be measured.

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

There are two main objectives in treating myeloma. These are to:

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

This is to control the myeloma itself. Treatment is usually most effective when two or more drugs are combined. These drugs have different but complementary mechanisms of action.

There are various anti-myeloma treatments available, which are used at different stages of myeloma and in different combinations. These include:

• steroids
• chemotherapy
• immunomodulatory drugs
• proteasome inhibitors
• monoclonal antibodies
• hHigh-dose therapy and stem cell transplantation.

Steroids are effective in killing myeloma cells. They are most commonly given in tablet form, but can also be given intravenously.

Side-effects can include stomach pain, raised blood sugar, increased appetite, change in mood, increased risk of infection and muscle weakness.

The most common steroids given are dexamethasone and prednisolone.

Chemotherapy (chemo) is the use of anti-cancer (cytotoxic) drugs to destroy cancer cells, and can be given as tablets, into a vein (‘intravenously’) or as an injection under the skin (‘subcutaneously’).

Side-effects can include nausea, vomiting, diarrhoea, sore mouth, infections and hair loss. Some chemotherapy drugs can cause infertility, if this is a consideration for you, you should speak to your doctor.

Examples of commonly used chemotherapies include cyclophosphamide and melphalan. These are most commonly given in tablet form or intravenously.

Thalidomide

Given as a tablet, usually in the evening. Side-effects can include constipation, drowsiness and peripheral neuropathy. Peripheral neuropathy is damage to the nerves in the hands and feet resulting in tingling, numbness, increased sensitivity and pain.

Lenalidomide (Revlimid) and Pomalidomide

Given as a tablet, usually in the evening.

Side-effects can include gastrointestinal disturbances, cramps, peripheral neuropathy and low blood count.

Bortezomib (Velcade)

Given as a subcutaneous injection in the chemotherapy day unit, or sometimes self-administered at home. Side-effects can include peripheral neuropathy, constipation and fatigue.

Carfilzomib

Given as an intravenous injection in the chemotherapy day unit. Side effects can include fatigue, heart damage and kidney damage.

Ixazomib

Given as a tablet that is taken once a week at home.

Daratumumab and Isatuximab

These are given as a subcutaneous or intravenous injection in the chemotherapy day unit. Side effects can include allergic reactions, and reduction on normal blood cell levels.

Intensive treatment involves giving a much higher dose of chemotherapy (melphalan). The aim of this treatment is 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 reduces the function of healthy bone marrow, stem cells are given via an infusion 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 (known as autologous transplantation). 

Intensive treatment is associated with significant side effects and requires a two- to three-week stay in hospital and a three- to six-month recovery period.

This is when anti-myeloma treatment is not required as the condition is not causing any symptoms or complications. This is sometimes referred to as asymptomatic or ‘smouldering myeloma’.

This can also happen once initial therapy is completed and the myeloma is under control. You will be actively monitored for signs and symptoms the cancer is beginning to cause problems.

It is important to understand that although myeloma is treatable, for most people it is not currently curable. This means that additional treatment is required when the cancer comes back.

When treatment is required again, the same principles are used as when treating newly diagnosed myeloma. Treatment is likely to be a combination of the anti-myeloma therapies described previously.

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.

Supportive care treatments are given to control and relieve complications and symptoms caused by myeloma. These include:

Bisphosphonates

Bisphosphonate medication can be used to help prevent bone damage and reduce the levels of calcium in your blood. The most commonly used are zoledronic acid (Zometa) and Pamidronate.

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.

Bisphosphonates are commonly given as an intravenous infusion. The most common side effects include fever and flu-like symptoms, nausea, impaired renal function. A rare side-effect is osteonecrosis of the jaw (ONJ), where bones of the jaw become damaged; you should let your dentist know that you are receiving bisphosphonates. You should speak to your myeloma team if you are finding any of these side effects troublesome.

Radiotherapy

Radiotherapy can be used to help relieve bone pain. It involves directing high-energy waves of radiation at bones that have been 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. This treatment can be used to reduce bone pain, or to treat a tumour which is compressing the spinal cord.

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.

Treatments for anaemia

If you have anaemia as a result of having a low number of red blood cells due to your myeloma or treatment, you may be given a blood transfusion.

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