Haematology - Multiple myeloma

Delayed diagnosis of this rare condition can increase the frequency of complications. By Dr Shirley D'Sa

Characteristic osteolytic lesions in the skull of a patient with myeloma (Photograph: Author images)
Characteristic osteolytic lesions in the skull of a patient with myeloma (Photograph: Author images)

Myeloma is a rare haematological malignancy, accounting for approximately 50 cases per million per year in the UK. The median age at presentation is 70 years, although a small number of patients may present before 50 years of age. Most patients present de novo, but a few develop from pre-existing monoclonal gammopathy of uncertain significance.

Clinical features
Patients commonly present insidiously with symptoms such as fatigue, bone pain and recurrent infections. Occasionally, they present acutely unwell and require emergency treatment.1

The clinical course of the disease can be extremely variable, with a median survival of three to five years. However, an increasing number of patients with myeloma survive for closer to 10 years, due to the availability of novel therapies such as lenalidomide and bortezomib.

Anaemia is present in 80 per cent of patients at diagnosis. Bone pain due to osteolytic lesions and pathological fractures is a frequent presenting feature (see image); half of patients have vertebral fractures and up to 30 per cent have non-vertebral fractures at diagnosis. Lytic lesions are found in 80-90 per cent of patients at presentation and 60 per cent have diffuse bone loss. Bone demineralisation, with renal impairment, may lead to hypercalcaemia. Renal impairment occurs in 20-30 per cent of patients at presentation.

In one-fifth of cases, only light chains may be produced (Bence-Jones myeloma) and in 5 per cent of cases, a monoclonal protein may be absent altogether (non-secretory myeloma); these circumstances may lead to pitfalls in making the diagnosis if the requisite tests (such as urine electrophoresis or imaging) are not done.

Myeloma cells typically reside within the bone marrow compartment of the axial skeleton and proximal long bones, where they induce osteolytic bone disease.

Since osteoblastic activity is suppressed, a bone scan is not a useful screening test for myeloma because it is typically negative.

Investigations
To screen for myeloma, the following investigations are required:

FBC: Normocytic normochromic anaemia (typically Hb 9-10g/dL) is usually present but Hb may be normal in asymptomatic myeloma. ESR: Typically markedly raised (often >100mm/h), but may be normal in non-secretory or light chain-only patients.

Renal function: May be normal; however, a raised urea and creatinine may herald significant renal deterioration and should be acted on promptly (immediate withdrawal of nephrotoxic drugs, referral for admission/ rehydration, treatment of associated hypercalcaemia).

Calcium and albumin: Hypercalcaemia is found in 30 per cent of patients at diagnosis.

Serum electrophoresis: To check for presence of paraprotein in the blood.

Serum immunoglobulin levels: Typically globally reduced in myeloma (immuneparesis), except for affected immunoglobulin subtype.

Urine electrophoresis: To check for light chains in urine (not dipstick, which does not detect light chains).

Imaging of symptomatic areas: Plain films or MRI (not bone scintigraphy).

Management
Only symptomatic patients require therapy. Following confirmation of the diagnosis by bone marrow examination and further imaging, younger, fitter patients (≤65 years) are treated with outpatient-based chemotherapy to reduce disease bulk, and then high-dose chemotherapy followed by autologous stem cell transplantation.

Older and less fit patients are treated with less intensive combinations of chemotherapy, which now include thalidomide as standard.

Such therapy usually achieves a remission duration of 12-18 months followed by disease progression, requiring further chemotherapy directed at inducing further remissions.

Guidelines for the management and supportive care of myeloma patients have recently been published.2

A GP's role
GPs have a key role to play in promoting a favourable outcome for patients with myeloma:

At diagnosis

  • Have a high index of suspicion for the disorder.
  • Initiate prompt and appropriate investigation of unexplained back pain, applying the red flags approach.3
  • Test urine as well as serum for a monoclonal protein.
  • Early referral to haematologist (consider the two-week rule).
Red flag triage for acute back pain

Red Flags

  • Age over 50 years and new back pain, or age under 20 years.
  • History of cancer.
  • Constitutional symptoms - fever, chills, weight loss.
  • Recent bacterial infection, such as UTI.
  • IV drug misuse.
  • Immune suppression.
  • Pain that worsens when supine, severe night-time pain, thoracic pain.
  • Structural deformity.

Management to consider if one or more flags are present

  • Check FBC, ESR, urinalysis.
  • If still concerned, consider referral or seek further clinical evidence with bone scan, X-ray or other laboratory tests.
  • Note that a negative X-ray alone does not rule out disease.

    During treatment

    • Quickly assess patients who are unwell on chemotherapy and consider the possibility of neutropenic sepsis.
    • Have a lower threshold for using antibiotics for the treatment of minor or moderate infections.
    • Consider the possibility of relapse if a patient off treatment develops new symptoms and refer back to treating haematologist.
    • Consider hyperviscosity syndrome if a patient develops confusion, headaches or visual disturbance; fundoscopy is a clue, showing tortuous, engorged retinal vessels.
    • In the event of new back pain, consider the possibility of spinal cord compression by checking for leg weakness and disturbance of bowel or bladder function.

    Symptom control

    • Liaise with the community symptom-control team and hospital-based haematology team about minimising symptoms such as pain, constipation and fatigue.
    • Avoid NSAIDs.
    • Consider gabapentin or pregabalin for neuropathic pain, a more frequent complication in myeloma patients owing to the use of novel therapies such as bortezomib.
    TEST YOUR HAEMATOLOGY KNOWLEDGE

    1. What are the presenting signs and symptoms of myeloma?

    2. What processes can contribute to renal impairment in myeloma patients?
    3. What is the outlook for myeloma patients in 2011?
    Click here to see the answers

    Conclusion
    Myeloma is a rare, incurable bone marrow cancer. However, in most cases, a response to chemotherapy can be achieved and with the appropriate use of sequential therapies, patients may live for many years. To maximise length and quality of life, early intervention with chemotherapy, radiotherapy and bisphosphonates should be the clinical goal in every symptomatic patient.

    GPs have a key role in investigating patients with persistent unexplained symptoms so that the diagnosis can be made promptly. In most cases, blood tests and imaging can reveal the condition, but occasionally, persistence is required, helped by an awareness of the pitfalls of the diagnostic process.

    • Dr D'Sa is a consultant haematologist at University College Hospital, London, and Mount Vernon Cancer Centre, Northwood

    Reflect on this article and add notes to your CPD Organiser on MIMS Learning

    CPD IMPACT: Earn More credits

    This further action point may allow you to earn more credits by increasing the time spent and the impact achieved.

    • Find more articles about haematology and questions on multiple myeloma at the haematology resource centre gponline.com/haematology

    References
    1. Blade J, Rosinol L. Hematol Oncol Clin North Am 2007; 21(6):1231-46, xi.

    2. British Committee for Standards in Haematology. Guidelines for supportive care in myeloma, 2010.

    3. McCarthy CJ, Gittins M, Roberts C et al. Spine 2007; 32(8): 921-6.

    Have you registered with us yet?

    Register now to enjoy more articles and free email bulletins

    Register

    Already registered?

    Sign in