Myeloma

Question 1

Summarise the pathophysiology of multiple myeloma.

Answer 1

Multiple myeloma (MM) arises from post-germinal B cells in the lymph node, with immunoglobulin (Ig) gene rearrangement, extensive somatic hypermutation, and class switching of immunoglobulin heavy chain (IgH) genes.

Normal Ig production is impaired, resulting in a relative hypogammaglobulinaemia. Conversely, an immunoglobulin known as paraprotein / M protein is overproduced (some patients produce the light chain component of paraprotein only).

Various chromosomal abnormalities are found in MM; translocations involving the immunoglobulin heavy chain (IgH) region at chromosome 14q32 are common.

MM is preceded by asymptomatic premalignant monoclonal gammopathy of undetermined significance (MGUS) tumours.

Question 2

List the 7 signs of multiple myeloma.

Answer 2

Osteolytic bone disease

Anaemia

Renal impairment (most common emergency - look for raised creatinine)

Total protein is often raised

Hypercalcaemia – not always

Other normal immunoglobulins are suppressed – we call this “immunoparesis”

Albumin is often low in advanced stage myeloma

Cord compression (uncommon)

Hyperviscosity syndrome (high levels of paraprotein - treat w/ plasma exchange)

*CRABI = hypercalcaemia, renal impairment, anaemia, bone pain, infection

Question 3

List the key diagnostic factors for multiple myeloma.

Answer 3

• M-protein in serum (electrophoresis) >30g/L (HIGH M-PROTEIN)
• And/or Bone marrow plasma cells >10% (EXCESS
  PLASMA CELLS)
• Related ORGAN damage (end organ damage
  CRABI = hypercalcaemia, bone lesions, renal
  insufficiency, anaemia, infections) (NB can have asymptomatic MM with no end organ damage)

Question 4

How does multiple myeloma cause bone damage?

Answer 4

MM does not damage bone directly - myeloma plasma cells upregulate expression of OPGL (stimulates osteoclasts) and downregulate expression of OPG (inhibits osteoclasts) by stromal cells

= increased bone resorption

Question 5

List the causes of renal impairment in multiple myeloma.

Answer 5

Light chain deposition in renal tubules leading to nephropathy ("myeloma kidney")
Dehydration
Infection
Hypercalacaemia
Uric acid
Amyloid 
Acute tubular necrosis also described

Question 6

List the treatments for multiple myeloma.

Answer 6

Supportive management – pain, anaemia, infections, radiotherapy, orthopaedics, anticoagulation

If pt can tolerate, chemotherapy should be given. Most common is Velcade (bortezomib - a proteasome inhibitor that interrupts ubiquitin recycling) in comb w/ thalidomide and dexamethasone.

Chemotherapy is given prior to stem cell transplant