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Multiple Myeloma

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Overview

Multiple myeloma (MM) describes the malignant proliferation of plasma cells leading to bone marrow infiltration, destruction, and failure. It also leads to the overproduction of a monoclonal immunoglobulin or immunoglobulin fragment (also known as paraprotein) from these malignant plasma cells. This can lead to the blood becoming overly viscous leading to complications.

Paraproteins found in the urine are known as Bence Jones proteins.

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at an increased risk of developing MM.

Epidemiology

  • MM is the second most common haematological cancer
  • The median age of presentation is 70 years
  • More common in men
  • More common in people of Afro-Caribbean descent
  • Incidence is 6.0 per 100,000

Risk Factors

  • MGUS
  • Family history
  • Exposure to mutagenic agents e.g. ionising radiation

Example History

A 65-year-old man has a 3-month history of back pain and fatigue with pallor.

Investigations:

Haemoglobin:78 g/L(130 – 180 g/L)
Platelets:312 x 109/L)(150 – 450 x 109/L)
Mean cell volume (MCV):(76.0 – 98.0 fL)
Urea:8.3 mmol/L(2.0 – 7.0 mmol/L)
Creatinine:230 µmol/L(55 – 120 µmol/L)

Presentation

The features of multiple myeloma can be remembered with the mnemonic CRAB IT:

  • Calcium raised:
    • MM leads to the overexpression of proteins that stimulate osteoclasts leading to bone breakdown and the release of calcium ions into the blood, causing hypercalcaemia (‘bones’, stones’ abdominal groans, psychiatric moans’):
      • Bones – bone pain, fractures
      • Stones – renal stones, polyuria, polydipsia
      • Abdominal groans – nausea, anorexia, constipation
      • Psychiatric moans – depression, insomnia, impaired memory, lethargy
  • Renal problems:
    • This is due to paraprotein deposition in renal tubules, damaging the kidneys:
  • Anaemia:
    • This occurs due to bone marrow infiltration. MM also suppresses haematopoiesis:
  • Bone problems:
    • Due to MM activating osteoclasts, hypercalcaemia, and infiltration of the bone marrow by malignant cells:
      • Pain – especially back pain
      • Pathological fragility fractures – particularly in the back
  • Infection:
    • This is due to large numbers of dysfunctional immunoglobulins:
      • Increased frequency and severity of infection
  • Thrombocytopenia:
    • This is due to bone marrow suppression:

Differential Diagnoses

Monoclonal gammopathy of undetermined significance (MGUS)

  • The patient is asymptomatic and has no end-organ damage (i.e. no CRAB IT features)
  • Serum electrophoresis shows increased levels of paraprotein. This is often identified incidentally.

Waldenström’s macroglobulinaemia (WM)

  • The patient has no bone pain
  • Features of WM include neurological and visual problems due to hyperviscosity, mucosal bleeding, hepatosplenomegaly, and lymphadenopathy 
  • Serum electrophoresis shows massively raised IgM (>30,000 mg/L)

Referral

  • Offer full blood count, calcium, plasma viscosity, and erythrocyte sedimentation rate in people ≥60 years with persistent bone pain, particularly back pain, or an unexplained fracture
  • Offer very urgent protein electrophoresis and a Bence-Jones protein urine test (within 48 hours) in people ≥60 years:
    • With hypercalcaemia or leukopenia and a presentation suggestive of myeloma or
    • With raised plasma viscosity or ESR and a presentation suggestive of myeloma
  • Refer using a suspected cancer pathway referral (within 2 weeks) if the results of protein electrophoresis or Bence-Jones protein urine test suggest myeloma

Investigations

All patients

  • Full blood count (FBC):
    • May show normocytic and normochromic anaemia
  • Urea and electrolytes (U&Es):
    • Urea and creatinine are usually increased
  • Serum calcium:
    • Hypercalcaemia may be present
  • Serum free light-chain assay:
    • May show increased concentration of free light chains in serum
  • Serum albumin:
    • Usually raised
  • Serum and urine protein electrophoresis:
    • Diagnostic test
    • Shows paraprotein spike e.g. raised IgG or raised IgA paraprotein spike
    • Shows hypogammaglobulinaemia except for the singular raised paraprotein
  • Whole-body imaging:
    • To identify osteolytic lesions
    • May be done with a CT, however, MRI whole-body MRI is being increasingly used
    • Essential in all patients with MM, shows osteolytic lesions and pathological fractures
  • Bone marrow aspiration and biopsy:
    • Diagnostic test
    • Shows monoclonal plasma cell infiltration

A diagnosis of MM is made using the International Myeloma Working Group criteria.

Management

Overview

Multiple myeloma is incurable and is chronic, relapsing, and remitting. Treatment involves induction therapy and maintenance therapy. This can involve the use of autologous stem cell transplants, bortezomib, and dexamethasone depending on patient characteristics.

Patients should be given an annual influenza vaccination.

Monitoring

  • Patients are monitored after treatment and recovery at least every 3 months
  • Laboratory tests are repeated at each follow-up to assess disease recurrence

Complications

Prognosis

  • The prognosis varies significantly, some people live >8 years post-diagnosis, and others die within 24 months
  • Patients who present acutely with severe symptoms have a worse prognosis

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