Multiple myeloma

Blood cells of all types are made in the bone marrow, which in adults occupies the central position of bones such as the vertebrae, ribs, pelvis and skull.

White blood cells are there to protect against infection and plasma cells make antibodies, which are specialised proteins capable of 'recognising' invading foreign substances or organisms - 'antigens'.

Multiple myeloma is a cancer of plasma cells that, as a result, make excessive amounts of antibody (termed paraprotein or 'M' band). In common with all cancers, the plasma cells in myeloma are identical ('clonal'), because they originate from a single abnormal cell that starts to multiply out of control. The protein produced is, therefore, also identical ('monoclonal' meaning the product of a single clone).

Multiple myeloma has three main effects.

First, it affects the bone marrow and the immune system, and can cause increased susceptibility to infection.

Second, it affects the skeleton and can cause localised damage (termed 'lytic lesions' - they are almost like holes punched in the bone where a local deposit of myeloma cells exists). These lesions are often painful and may predispose to fracture or crushing of the bone.

Thirdly, multiple myeloma can cause damage to the kidneys, as a consequence of a variety of mechanisms (see below).

It is the commonest form of cancer of blood cells, accounting for 15 per cent of all blood cancers. There are about 2500 new cases per annum in the UK, giving rise to 10-15,000 patients with the condition at any one time. The overall incidence is rising, and is higher in Afro-Caribbeans.

Multiple myeloma is treatable, but it cannot be considered a curable condition.

How does one develop myeloma?

The cause of myeloma is not known. It is not inherited and it is not contagious. In common with other blood cancers there is an increased incidence in patients exposed to radiation.

Organic-chemical exposure may increase incidence, but there are no clear data.

A recent report suggests that multiple myeloma patients have a higher incidence of infection (up to 80 per cent or more) by a human herpes virus (HHV8) than do normal subjects (up to 25 per cent); these reports are unconfirmed.

The cancer process

Our concept of bone marrow cancer is that it is a multi-step process, involving multiple alterations to cells, which turn into cancer cells.

The plasma cells of multiple myeloma proliferate (multiply) in an uncontrolled way. Normal plasma cells also proliferate as they go from early immature forms to that of the fully functional cell, principally when they are stimulated to produce antibodies following exposure to an antigen. This cell-antigen interaction occurs outside the marrow (eg in lymph glands) and is controlled by chemicals called cytokines secreted by other cells.

Cells such as lymphocytes, bone marrow stromal cells, other plasma cells, and the cells which make and break down bone (osteoclasts and osteoblasts) all play a part in controlling this process and the consequent plasma cell proliferation but in a healthy person the controlling process works perfectly. In multiple myeloma, abnormal cells circulate and then settle in the marrow or other parts of the skeleton, where they proliferate.

Some of the cytokines involved in this process include tumour necrosis factor (TNF), interleukin-1 beta (IL1-b) and interleukin-6 (IL6). IL6 seems particularly important in promoting the growth of plasma cells.

Changes observed in myeloma cells

Myeloma cells differ from normal plasma cells in a number of ways. Knowledge of these differences helps us to distinguish malignant cells from normal and may yield clues to the processes involved when normal cells 'transform' to malignant ones.

What is the general behaviour of multiple myeloma?

Most patients with multiple myeloma develop symptoms of the condition over a period of a few weeks or months.

Some (less than 10 per cent) may have already been found to have an abnormal protein (paraprotein) in their blood, perhaps by chance through routine investigation and are therefore under medical supervision. They might then develop an alteration in their condition, such as a bone lesion, and then need to begin therapy. Not everyone with an abnormal paraprotein has myeloma and not everyone with myeloma requires treatment.

Once treatment is commenced, patients are followed up regularly and monitored carefully. More than 75 per cent of patients will respond to therapy, and the level of the abnormal protein will fall. In less than a third of patients the paraprotein disappears completely (typically in response to more intensive therapy), thus the patient achieves a 'complete remission'.

A characteristic feature of multiple myeloma is that the disease enters a stable, or 'plateau' phase - during which time the patient is well, requires no treatment, and measurable disease indicators are stable. This phase typically lasts 12 to 40 months but it can be 10 to 15 years or more. Unfortunately, some patients deteriorate before ever reaching a stable phase.

In most patients the disease eventually becomes active again ('relapses'), and then it is more difficult to treat, possibly ending in the person's death.

What are the symptoms and signs?

The most important consequences of myeloma are described below.