Myeloma Flashcards

1
Q

Myeloma is a type of cancer affecting which cells? [1]

A

Plasma cells - B lymphocytes that produce antibodies (aka immunoglobulins)

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2
Q

Describe the pathophysiology of myeloma [2]

A

Myeloma is a cancer of single type of plasma cell with a genetic mutation that causes them to divide uncontrollably: as a result they produce a specific paraprotein - aka M protein; am abnormal antibody / immunoglobulin. There is a abnormal high level, this is called paraproteinaemia

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3
Q

Describe the three stages in myeloma pathophysiology [3]

A

First: Development of monoclonal gammopathy of undetermined signficicance (MGUS)
- Precancerous phase
- Initial cytogentic abnormality occurs (inciting event) due to abnormal plasma cell response to a stimulus
- Causes creation of a plasma cell clone that secretes monoclonal antibody paraprotein
- Most don’t develop to MM

Second: Smouldering myeloma
- involves abnormal plasma cells and paraproteins but no organ damage or symptoms
- It has a greater risk of progression to myeloma (about 10% per year).

Third: MGUS to MM
- Further cytogenic abnormalities
- Myeloma affects multiple bone marrow areas in the body.

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4
Q

What is important to note about the prognosis of MGUS? [1]

A

MGUS is often an incidental finding in an otherwise healthy person. It has a small risk of progression to myeloma (about 1% per year).

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5
Q

What is meant by the term paraproteinaemia? [1]

A

plasma cells become abnormal, multiply uncontrollably and produce a large amount of a single type of antibody (known as paraprotein or M-protein) which has no useful function

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6
Q

Describe the clinical features of myeloma [6]

A

CRABBI

C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain
B - Bleeding
I - Infection

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7
Q

Describe the reasons for the following presentations in MM [6]

C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain
B - Bleeding
I - Infection

A

C – Calcium (elevated)
- Hypercalcaemia
- Increased osteoclasts activity due to cytokine activation released by myeloma cells

R – Renal failure
- Immunoglobulin light chain deposition within renal tubules

A – Anaemia
- Suppresed erythropoeisis

B – Bone lesions and bone pain
- Increased osteoclast activity causes lytic bone pain

B - Bleeding
- Due to thrombocytopenia

I - Infection
- Reduction in normal immunoglobulins

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8
Q

Describe the anaemia seen in MM [1]

A

Normocytic and normchromic

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9
Q

Aside from CRABBI, name 5 extra features to be aware of in MM [5]

A

Amyloidosis - e.g. macroglossia

CTS

Spinal cord compression

Neuropathy

Hyperviscosity

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10
Q

Describe the typical presentation of hyperviscosity syndrome in MM [5]

What is the classic triad? [3]

A

Hyperviscosity syndrome is considered an emergency. It can cause many issues:

Triad:
- neurologic abnormalities
- vision changes
- mucosal bleeding

  • Blurred vision
  • Headaches
  • Mucosal bleeding
  • Dysopnoea due to HF
  • Neurological syndromes
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11
Q

Describe what is meant by ‘plasmocytomas’ [1]

A

Plasmacytomas are individual tumours formed by cancerous plasma cells. They can occur in the bones, replacing normal bone tissue, or in the soft tissues.

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12
Q

Describe the typical presentation of a MM patient [7]

A

Persistent bone pain (e.g., spinal pain)
Pathological fractures
Unexplained fatigue
Unexplained weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment

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13
Q

Describe the NICE referral criteria for MM [3]

A
  • 60+; persistent bone pain, especially in the back
  • 60+; hypercalcaemia or leukopenia with a presentation consistent with MM
  • Plasma viscosity and ESR consistent with MM
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14
Q

What test would you conduct for the following patients?

  • 60+; persistent bone pain, especially in the back [3]
  • 60+; hypercalcaemia or leukopenia with a presentation consistent with MM [2]
  • Plasma viscosity and ESR consistent with MM [2]
A

60+; persistent bone pain, especially in the back:
- FBC; including Ca, plasma viscosity and ESR

60+; hypercalcaemia or leukopenia with a presentation consistent with MM
- Protein electrophoresis and a Bence-Jones protein urine test

Plasma viscosity and ESR consistent with MM
- - Protein electrophoresis and a Bence-Jones protein urine test

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15
Q

Describe what is meant by protein electrophoresis and a Bence-Jones protein urine test

A

Bence Jones protein refers to free light chains in the urine.

protein electrophoresis: test that measures specific proteins in the blood

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16
Q

A person has suspected MM.

A blood smear is performed and this is shown.

What is the name of the abnormality seen? [1]

A

Roleaux formation

17
Q

Which Igs are most likely to be found raised in serum protein electrophoresis [2]

A

IgA/IgG

18
Q

Serum-free light-chain assay would be indicated to specifically detect what? [1]

A

abnormally abundant light chains

19
Q

What is used for the definitive diagnosis of MM? [1]

A

Bone marrow biopsy

20
Q

Imaging is used to assess for bone lesions. The order of preference is? [3]

A
  • Whole-body MRI
  • Whole-body low-dose CT
  • Skeletal survey (x-ray images of the entire skeleton)
21
Q

What skull change indicates MM? [1]

A

Raindrop skull (similar to pepper pot skull in primary hyperparathyroidism) refers to multiple lytic lesions seen in the skull on an x-ray.

22
Q

Typical x-ray changes seen in patients with myeloma include? [3]

A
  • Well-defined lytic lesions (described as looking “punched-out”) e.g. Raindrop skull
  • Diffuse osteopenia
  • Abnormal fractures
23
Q

What is the diagnostic criteria for MM? [3]

State the investigational technqiues that can be used for each of the above

A

Identifying a monoclonal antibody / M protein
- Protein electrophoresis
- Serum free light chains
- Urine electrophoresis for Bence-Jones protein

Bone marrow analysis
- Bone marrow aspirate and cytogenetics

Assessing organ damage
- FBC
- U&E
- Bone profile
- Imaging: MRI; CT; skeletal survey

24
Q

What are the major and minor criteria for diagnosis of MM?

How many do you need of each? [1]

A
25
Q

Describe the four stages to MM tx [4]

A
  • induction therapy
  • autologous stem cell transplantation (ASCT)
  • maintenance therapy
  • managing relapse or refractory disease.
26
Q

Describe the four stages to MM tx [4]:

  • induction therapy
  • autologous stem cell transplantation (ASCT)
  • maintenance therapy
  • managing relapse or refractory disease.
A

Induction therapy:
- Usually combination of three drugs:
* targeted drugs (such as thalidomide, lenalidomide, bortezomib, daratumumab)
* chemotherapy (such as cyclophosphamide or melphalan)
* steroids (such as prednisolone or dexamethasone)

Autologous stem cell transplantation (ASCT)
- removal of a patient’s own stem cells prior to chemotherapy, which are then replaced after chemotherapy
- Stem cell transplantation can be: Autologous (using the person’s own stem cells) or Allogeneic (using stem cells from a healthy donor)

Maintenance therapy:
- bortezomib or lenalidomide
- Typically given until progression.

Managing relapse or refractory disease:
- almost all patients will relapse,

27
Q

pathological fractures: [] is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.

A

pathological fracture: zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.

28
Q

Which complications need to be managed in MM? [5]

Describe the treatment used to manage these complications [+]

A

pain:
- treat with analgesia (using the WHO analgesic ladder)
- Radiotherapy for bone lesions can improve bone pain

pathological fracture:
- zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.

infection
- patients receive annual influenza vaccinations
- they may also receive Immunoglobulin replacement therapy.

venous thromboembolism prophylaxis

fatigue
- if symptoms persist consider an erythropoietin analogue.

29
Q

Describe the typical presentation of MM bone disease [2]

A

Bone pain

Fractures of vertebral bodies - related to osteolytic bone lesions

30
Q

Describe the specific managment for myeloma bone disease [5]

A

Bisphosphonates to suppress osteoclast activity

Radiotherapy for bone lesions can improve bone pain

Orthopaedic surgery to stabilise bones (e.g., by inserting a prophylactic intramedullary rod) or treat fractures

Cement augmentation (injecting cement into vertebral fractures or lesions) to improve spine stability and pain

31
Q

What is used as a prognostic tool for myeloma? [1]

A

Beta-2 microglobulin levels

32
Q

What are the different stages for MM prognosis that are based off beta-2 microglobulin levels [3]

A

Stage I: median survival 62 months
Stage II: median survival 44 months
Stage III: median survival of 29 months

33
Q

How do you differentiate between benign paraproteinaemia and myeloma? [1]

A

MGUS:
- absence of myeloma-related organ or tissue damage (predominantly renal, skeletal or bone marrow impairment).

Patients are often elderly and in good health.

34
Q

Describe overall treatment plan for myelomas [3]

A
35
Q
A