Multiple Myeloma Flashcards

1
Q

What is the mnemonic for multiple myeloma?

A

CRAB

Calcium elevation
Renal insufficiency/kidney impairment
Anaemia
Bone disease

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2
Q

What are the subtypes of multiple myeloma?

A

50% IgG
20% IgA
20% kappa or lambda light chain

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3
Q

What causes anaemia in multiple myeloma?

A

Dilution by M/paraprotein
BM replacement
Relative EPO deficiency (in part due to kidney damage)

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4
Q

What is multiple myeloma?

A

A haematological cancer characterised by clonal proliferation of plasma cells in the bone marrow and presence of a monoclonal immunoglobulin (or fragment) in the serum and urine

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5
Q

What are the most common presenting features of MM?

A

Bone pain and anaemia

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6
Q

Are males or females more likely to get MM?

A

Men

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7
Q

What is the typical age of diagnosis of MM?

A

69

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8
Q

What is the pathophysiology of MM?

A

Arises from post-germinal B cells in the lymph node with extensive somatic hypermutation and class switching of heavy chain genes suggesting that the plasma cells have undergone antigen selection

MM cells usually secrete Ig or Ig fragments in urine or plasma

However, normal Ig is impaired so you have a relative hypogammaglobulinaemia and are predisposed to infections

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9
Q

What is the common translocation mutation involved in MM?

A

14q32

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10
Q

What mutation is associated with a poor prognosis in MM?

A

Chr 17p deletion
Chr 13 deletions

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11
Q

What is the pathogenesis of bone disease?

A

Adhesion molecules mediate the homing of myeloma cells to the bone marrow and adhesion to BM stromal cells and ECM.

Cytokines stimulate osteoclastgenesis and osteoclast activity + impair osteoblast formation –> osteolytic bone disease and hypercalcaemia

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12
Q

What are the symptoms of hypercalcaemia?

A

Bones, stones, groans, psychiatric moans

Bone pain
Kidney stones
Abdominal groans (constipation, nausea, indigestion)
Psychiatric moans: depression, memory loss

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13
Q

When is MM suspected?

A
  • Bone pain with lytic lesions
  • Increased total serum protein concentration and/or the presence of monoclonal (M) protein in the serum or urine
  • Systemic signs suggestive of malignancy e.g. unexplained anaemia
  • Hypercalcaemia
  • Acute kidney failure
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14
Q

What are the diagnostic criteria of MM?

A
  1. Clonal BM plasma cells >10%

PLUS one of the following

  • Presence of related organ or tissue impairment (CRAB)
  • Presence of a biomarker associated with near inevitable progression to end organ damage (SLiM = sixty, light chain ratio, MRI)
    >60% clonal plasma cells in BM
    FLC ratio of 100 or more
    MRI with more than one focal lesion
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15
Q

What are the symptoms of MM?

A

Anaemia
Bone pain
Infections
Fatigue (anaemia or hyperCa)
Renal impairment

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16
Q

What Ix do you do for MM?

A

Routine UA

FBC- anaemia

Serum calcium, creatinine, albumin, LDH, beta2 microglobulin (B2M) (helpful for prognosis)

Serum/urine protein electrophoresis: serum M protein elevated (IgG or IgA)

Serum/urine immunofixation: to determine the paraprotein immunoglobulin type: IgG, IgA or kappa or lamba light chain are most common)

Serum free light chain assay (FLC assay) increased

BM aspirate and biopsy: immunophenotyping, cytogenetics

Whole body low dose CT or MRI

17
Q

What are some of the major toxic complications for MM?

A

Infective episodes (rarely sepsis)
DVT (use aspirin or a NOAC)
Neuropathy

18
Q

What are the general management considerations of MM?

A

Ensure treatment of bone disease (bisphosphonates or denosumab)
Analgesia
Hydration to prevent renal failure
DVT prophylaxis

1st line= stem cell transplant

2nd line= use of the induction drugs + maintenance regime
- Dexamethasone, thalidomide, bortezombib etc

3rd line = combination and novel agents
- Carfilzomib
- isatuximab

18
Q

What is the management for stem cell transplant of MM?

A

Stem Cell Transplant!

1st line; induction therapy
- Non-chemo more popular: dexamethasone, thalidomide, bortezomib etc

Conditioning; melphalan
Stem cell transplant