Multiple myeloma

Clinical features, investigations, management and the GP's role in this rare haematological malignancy.

Coloured X-ray of the skull of a patient with myeloma, showing multiple lesions (dark grey and dark blue) (Photo: SPL)
Coloured X-ray of the skull of a patient with myeloma, showing multiple lesions (dark grey and dark blue) (Photo: SPL)

Multiple myeloma is a clonal B cell malignancy characterised by proliferation of plasma cells that usually secrete monoclonal immunoglobulin or light chains (kappa or lambda). It is a rare haematological malignancy, accounting for 1% of all malignancies, and has an incidence of four per 100,000 per year.

The median age at presentation is 66 years, with less than 3% of patients being under 40 years of age.1

Most patients present de novo, but it is now recognised that in virtually all patients, myeloma is preceded by the asymptomatic condition monoclonal gammopathy of uncertain significance (MGUS).2

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.

Emergencies in myeloma patients can include hyperviscosity syndrome (due to increased serum immunoglobulin), hypercalcaemia, spinal cord compression, bone fractures or acute kidney injury.2

Anaemia is present in 70% of patients at diagnosis.3 Bone pain is present in up to 58% of patients and is due to osteolytic lesions and pathological fractures (see image). Lytic lesions are found in 80-90% of patients at presentation.4 Bone demineralisation, with renal impairment, may lead to hypercalcaemia. Renal impairment occurs in 20-30% of patients at presentation.5

In 20% of cases, only light chains may be produced (light chain-only myeloma) and in 5% of cases, a monoclonal protein may be absent altogether (non-secretory myeloma).2 These circumstances may lead to pitfalls in making the diagnosis if the requisite tests (such as urine electrophoresis or imaging) are not carried out.

Myeloma cells typically reside within the bone marrow compartment of the axial skeleton and proximal long bones, where they induce osteolytic bone disease. Osteoblastic activity is suppressed, so bone scan is not a useful screening test for myeloma because it is typically negative.


To screen for myeloma, the following investigations are required:2

  • FBC Normocytic normochromic anaemia (typically Hb 90-100g/L) 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% of patients at diagnosis. Albumin may be low and is a poor prognostic sign
  • Serum protein electrophoresis with immunofixation To check for the presence of a paraprotein in the blood
  • Serum immunoglobulin levels Typically globally reduced in myeloma (immune paresis), except for the affected immunoglobulin subtype
  • Urine protein electrophoresis To check for light chains in urine (not urine dipstick or urine protein creatinine ratio, because this will not specifically detect the paraprotein or light chains)
  • Skeletal survey This is the screening technique of choice and should include a postero-anterior (PA) view of the chest, anteroposterior (AP) and lateral views of the cervical spine, thoracic spine, lumbar spine, humeri and femora, AP and lateral view of the skull, and AP view of the pelvis
  • Imaging of symptomatic areas Plain films or MRI (not bone scintigraphy)


Only symptomatic patients require therapy, although there is increasing evidence that we should treat high-risk smouldering myeloma to delay progression to active disease and improve overall survival.6 Symptomatic myeloma is defined by the presence of myeloma-related organ and tissue impairment (ROTI), manifested by the CRAB criteria (calcium, renal failure, anaemia, bone lesions).

Following confirmation of the diagnosis by bone marrow biopsy and further imaging, fitter, younger patients (≤65 years) are treated with outpatient-based chemotherapy to reduce disease bulk, 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 patients with myeloma have recently been published.2

The GP's role

GPs have a key role in promoting a favourable outcome for patients with myeloma at diagnosis and during treatment.

At diagnosis, GPs should:

  • Have a high index of suspicion for the disorder
  • Initiate prompt and appropriate investigation of unexplained back pain, applying the red flags approach7
  • Test urine as well as serum for a monoclonal protein
  • Ensure early referral to a 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 pain at night, thoracic pain
  • Structural deformity

Management to consider if one or more flags are present

  • Check FBC, ESR, U&Es, bone profile, serum and urine protein electrophoresis
  • If still concerned, consider referral or seek further clinical evidence with bone scan, X-ray or other laboratory tests (such as serum free light chains)
  • Note that a negative X-ray alone does not rule out disease

During treatment, GPs should:

  • 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 the 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

In managing symptom control, the GP should:

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


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 the diagnosis can be made promptly. As with other types of cancer, the outcome depends on how advanced the disease is at diagnosis. Early referral is important for favourable disease outcomes, but also to safeguard the skeleton and maintain a good quality of life.

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 Attwood is specialist registrar in haematology, University College Hospital, London; Dr D'Sa is a consultant haematologist, University College Hospital, London and Mount Vernon Cancer Centre, Middlesex

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  1. Kyle RA, Rajkumar SV. Epidemiology of the plasma cell disorders. Best Practice Res Clin Haematol 2007; 20: 637-64
  2. Bird JM, Owen RG, D’Sa S et al. The diagnosis and management of multiple myeloma. British Committee for Standards in Haematology. 2014
  3. Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clinic Proc 2005; 80: 1371-82
  4. Palumbo A, Anderson K. Medical progress: multiple myeloma. N Engl J Med 2011; 364: 1046-60
  5. Eleutherakis-Papaiakovou V, Bamias A, Gika D et al. Renal failure in multiple myeloma: incidence, correlations and prognostic significance. Leuk Lymph 2007; 48: 337-41
  6. Mateos M-V, Hernandez M-T, Giraldo P et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med 2013; 369: 438-47
  7. McCarthy CJ, Gittins M, Roberts C et al. The reliability of the clinical tests and questions recommended in international guidelines for low back pain. Spine 2007; 32(8): 921-6

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