Multiple Myeloma

• Multiple myeloma is a disease of plasma cells:

  • One particular plasma cell clone begins to replicate in an uncontrolled manner , resulting in one specific type of immunoglobulin being overproduced
  • The spike in a specific form of immunoglobulin can be seen as a monoclonal band on serum and urine electrophoresis
• Complications:

  ·       Plasma cell clones accumulate in the bone marrow resulting in anaemia, immune suppression and low platelets

  ·       Abnormal plasma cells produce paraprotein which cause damage to the kidneys

  ·       Abnormal plasma cells secrete factors which activate osteoclasts to break down bone resulting in widespread lytic lesions, bone pain and hypercalcaemia
• IgG is the most common form of multiple myeloma - around 2/3 of cases

  IgA accounts for around 1/3 of cases
• Multiple myeloma is the second most common haematological malignancy in the UK. It is more common in men than in women and incidence increases with age.
• Bone pain is the most common feature:

  • Most commonly in the spine and ribs
  • Typically worsens with activity
  • Pain occurs due to increased osteoclast activity within the bones creating lytic lesions
  • Hypercalcaemia develops due to the reabsorption of bone
• Production of red cells and platelets is inhibited by plasma cells invading the bone marrow resulting in anaemia and thrombocytopaenia

  • Anaemia - SOB and fatigue
  • If platelets reach critically low levels symptoms such as petechiae, bruising and bleeding develop
• Renal failure:

  • Uraemia - nausea and vomiting
  • Increased phosphate - pruritis and muscle cramping
  • SOB and oedema secondary to inability to excrete fluids
• Patients with multiple myeloma are significantly immunocompromised as the immunoglobulin is mutated and ineffective - often present with respiratory or urinary infections
• multiple myeloma can cause spinal cord compression due to the lytic lesions from increased osteoclast activity

  Patients with limb weakness and loss of bladder/bowel control should be seen urgently
• Investigations:

  • FBC - anaemia, neutropoenia and thrombocytopaenia
  • U&Es - raised creatinine and hypercalcaemia (check PTH)
  • ESR - raised
  • LDH - raised due to increased cell turn over
  • Blood film - rouleaux formation - red cells stacked on top of each other
  • Immunoglobulin measurement
  • Protein electrophoresis of blood and urine - Bence Jones protein
  • Free light chain levels
• • Symptoms of multiple myeloma may include:
  • Bone pain, often in the lower back.
  • Fatigue.
  • Confusion, muscle weakness, constipation, thirst, and polyuria (due to hypercalcaemia).
  • Weight loss.
  • Recurrent infection.
  • Headache, visual disturbance, cognitive impairment, mucosal bleeding, and breathlessness (due to hyperviscosity of the blood).
  • Sensory loss, paraesthesia, limb weakness, walking difficulty, and sphincter disturbance (due to spinal cord compression).
• Patients with blood findings and symptoms consistent with multiple myeloma should have have urgent protein electrophoresis of blood and urine, bence jones protein and free light chain levels:

  • Paraprotein band on electrophoresis
• Considering arranging X-rays of symptomatic areas to rule out pathological fractures
• Secondary care investigations:

  • Bone marrow biopsy
  • MRI - confirm the extent of disease
• · With high dose chemotherapy followed by autologous stem cell transplantation, the median survival has been estimated to be 4.5 years.

  · The overall 5-year survival rate is around 35%.
• Skeletal survey:

  • Series of x-rays of the skull, axial skeleton and proximal long bones
  • Looking for the typical lesions of multiple myeloma
  • MRI is more sensitive at detecting lytic lesions
• Once patients have have received induction chemotherapy and stem cell transplant they receive maintenance treatment with regular chemotherapy. The disease almost always relapses at some point.
• Refer people using a suspected cancer pathway referral if the results of protein electrophoresis or a Bence-Jones protein urine test suggest myeloma