Myeloma

At diagnosis, 70% of patients have pain of varying intensity associated with lytic bone lesions. The most common sites of pain are the lower back and ribs.

Back pain is very common in the general population and so often the diagnosis is delayed.

Symptoms may include:

• Bone related symptoms – backache, loss of height, pathological fractures, spinal cord compression.
• Frequent chest infections in particular pneumonia
• Bone marrow failure symptoms – anaemia related breathlessness /lethargy, bleeding and bruising.
• Hyperviscosity symptoms – headaches, visual disturbances, pins and needles in extremities.

Detection of a paraprotein in the blood/urine is not sufficient to give a diagnosis of multiple myeloma.

Other conditions such as monoclonal gammopathy of unknown significance (MGUS) and lymphoma can also give rise to a paraprotein.

Rarely a paraprotein is not detectable and these patients are said to have non-secretory myeloma.

The diagnosis depends on:

• Bone marrow containing more than 10% plasma cells.
• Myeloma related organ or tissue impairment- lytic bone lesions, renal impairment, hypercalcaemia, anaemia.

The hallmark of MGUS is the presence of a paraprotein coupled with the absence of a bone marrow plasma cell infiltrate or myeloma related organ or tissue impairment.

Patients with an increase in bone marrow plasma cells but no evidence of myeloma related organ damage are said to have Asymptomatic myeloma.

The survival of patients with Asymptomatic myeloma is considerably longer than patients with myeloma related organ or tissue impairment.

Diagnostic tests

1. Serum electrophoresis/immunofixation – measuring the amount of the paraprotein in the blood or urine is of value in monitoring the response to treatment.
2. Serum free light chain assay – detects fragments of paraprotein called free light chains. Particularly valuable where no paraprotein can be detected in the blood/urine. Also allows prediction of whether patients with MGUS are likely to progress to multiple myeloma.
3. Bone Marrow Aspiration.
4. Skeletal survey – 70% of patients will have detectable punched out lytic bone lesions.
5. MRI spine – useful for detecting local areas of damage within the bones of the spine.

Asymptomatic myeloma – studies have shown that there are no benefits from early treatment of these patients.

Patients with myeloma related organ or tissue impairment – treatment can be divided into:

• Supportive measures.
• Definitive treatment of the underlying disease.

Supportive measure

Aims to maintain patients’ quality of life by preventing problems such as kidney failure, infection and helping control bone disease.

• All patients with myeloma must maintain a fluid intake of at least 3 litres daily to prevent dehydration
• Avoid non-steroidal anti-inflammatory drugs such as ibuprofen or diclofenac
• Annual flu vaccination
• Treatment of anaemia with blood transfusion or erythropoietin injections
• Bisphosphonates – bind to the surface of bones and markedly reduce skeletal damage and help prevent bone pain, hypercalcaemia and pathological fractures. Clinical studies have shown that maximum benefit is achieved when bisphosphonates are given before there is evidence of bone damage. The main bisphosphonates currently used are pamidronate or zoledronic acid (Zometa) which are given by monthly infusion into a vein.

Definitive treatment of the underlying disease

Chemotherapy

Younger fitter patients will receive combination chemotherapy with the aim of eliminating all detectable signs of the disease both clinically and by laboratory tests. This is called a complete response.

This may be followed by a stem cell transplant carried out using the patient’s own stem cells known as an autologous transplant.

More elderly patients may be treated with more gentle chemotherapy regimes aimed at achieving a stable response without any attempt to eradicate the disease.

Thalidomide

Thalidomide was used briefly in the 1950s for prevention of morning sickness during pregnancy. It was withdrawn from the market because it was found to cause severe congenital limb development abnormalities.

Under stringent control it was re-introduced for the treatment of multiple myeloma as it is effective in preventing new blood vessel formation and also modifies the behaviour of the immune system.

The MRC UK Myeloma IX study showed the combination of cyclophosphamide, thalidomide and dexamethasone to be most effective in the first line treatment of patients with Multiple myeloma.