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.
Pain Typically back pain or sometimes pain in a limb due to a localised deposit of myeloma within the bone (a 'lytic lesion'). The pain might be dull and spread over a general area when due to infiltration of the bone marrow or skeleton, or it might be well localised to a local tumour deposit. The affected bone may fracture or crush, causing severe pain. If a fracture occurs in the spine of the neck, chest or upper lumbar region, the damaged bone may press upon the spinal cord and cause neurological symptoms (eg pain or numbness in the abdomen or legs, or incontinence).
Bone marrow failure The presence of the great numbers of abnormal plasma cells reduces the bone marrow's capacity to make normal blood cells, causing anaemia (reduced red cells), infection (reduced white cells) or bruising and bleeding (reduced platelets).
Â Anaemia can occur for a number of reasons. It occurs in anyone who is unwell, particularly when suffering from cancer or infection (so-called 'anaemia of chronic disease'). Myeloma can cause loss of appetite and weight loss, which may partly be due to increased levels of cytokines in the blood. Later in the course of the disease, anaemia can result from the development of kidney failure as the kidneys have an important role in the manufacture of blood. Myeloma treatment can also cause anaemia.
Infection This can occur due to a number of factors. In addition to reduced white cells, myeloma patients lack normal levels of functional antibodies in the blood, and so are less equipped to deal with antigens. Such infections are typically due to bacteria (urinary tract, skin and chest infections) or viruses (colds, flu, shingles). The paraprotein can also interfere with the process of engulfment of bacteria by white cells (phagocytosis).
Kidney failure If the paraprotein produced by the plasma cells is of a smaller molecular size it may get through the first part of the kidney's filtering mechanism and then silt up the rest of the fine network of tubes (tubules) within the kidney, leading to kidney failure. These small paraproteins are known as Bence Jones protein, or 'light chains'. Most light chain production occurs alongside that of the larger molecules produced by the abnormal plasma cells, but in 20 per cent of people with myeloma, light chains only are produced. This is important because in the latter there is no abnormal paraprotein in the blood, and the diagnosis can be made only if the urine is checked for the presence of light chains. Other causes of kidney damage in myeloma include the increased blood level of calcium (due to skeletal damage), infection and, later in the course of the disease, as a side effect of some of the drugs required to treat myeloma.
o Amyloidosis is a condition related to myeloma. In one type (AL amyloid) a clone of malignant cells make only part of an antibodyterm molecule (the light chain), which can be deposited in a range of tissues to cause damage. These tissues include kidney, heart, liver, skin and nerves.
o Paraprotein binding to nerves causes sensory problems (numbness, tingling) or, more rarely, motor problems (inability to move a muscle or group of muscles).
o The paraprotein can interfere with the function of white blood cells and can stop platelets from working properly, increasing the likelihood of bruising and bleeding.
o An increased concentration of circulating protein in the blood can increase the volume of plasma that the heart has to pump around, and this can cause 'heart failure'. It can also increase the thickness of the blood (viscosity), particularly if it is a type of myeloma resulting in production of a large antibody (IgM or IgA rather than IgG). Normal blood is about twice as viscous as water, whereas blood in this type of myeloma may be five or six times more viscous than water. Blood flow in the small arteries of the eye and brain is therefore impaired, which can cause visual symptoms (blurred vision), headaches and confusion.