Myeloma Flashcards
Myeloma is a type of cancer affecting which cells? [1]
Plasma cells - B lymphocytes that produce antibodies (aka immunoglobulins)
Describe the pathophysiology of myeloma [2]
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
Describe the three stages in myeloma pathophysiology [3]
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.
What is important to note about the prognosis of MGUS? [1]
MGUS is often an incidental finding in an otherwise healthy person. It has a small risk of progression to myeloma (about 1% per year).
What is meant by the term paraproteinaemia? [1]
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
Describe the clinical features of myeloma [6]
CRABBI
C – Calcium (elevated)
R – Renal failure
A – Anaemia
B – Bone lesions and bone pain
B - Bleeding
I - Infection
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
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
Describe the anaemia seen in MM [1]
Normocytic and normchromic
Aside from CRABBI, name 5 extra features to be aware of in MM [5]
Amyloidosis - e.g. macroglossia
CTS
Spinal cord compression
Neuropathy
Hyperviscosity
Describe the typical presentation of hyperviscosity syndrome in MM [5]
What is the classic triad? [3]
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
Describe what is meant by ‘plasmocytomas’ [1]
Plasmacytomas are individual tumours formed by cancerous plasma cells. They can occur in the bones, replacing normal bone tissue, or in the soft tissues.
Describe the typical presentation of a MM patient [7]
Persistent bone pain (e.g., spinal pain)
Pathological fractures
Unexplained fatigue
Unexplained weight loss
Fever of unknown origin
Hypercalcaemia
Anaemia
Renal impairment
Describe the NICE referral criteria for MM [3]
- 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
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]
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
Describe what is meant by protein electrophoresis and a Bence-Jones protein urine test
Bence Jones protein refers to free light chains in the urine.
protein electrophoresis: test that measures specific proteins in the blood
A person has suspected MM.
A blood smear is performed and this is shown.
What is the name of the abnormality seen? [1]
Roleaux formation
Which Igs are most likely to be found raised in serum protein electrophoresis [2]
IgA/IgG
Serum-free light-chain assay would be indicated to specifically detect what? [1]
abnormally abundant light chains
What is used for the definitive diagnosis of MM? [1]
Bone marrow biopsy
Imaging is used to assess for bone lesions. The order of preference is? [3]
- Whole-body MRI
- Whole-body low-dose CT
- Skeletal survey (x-ray images of the entire skeleton)
What skull change indicates MM? [1]
Raindrop skull (similar to pepper pot skull in primary hyperparathyroidism) refers to multiple lytic lesions seen in the skull on an x-ray.
Typical x-ray changes seen in patients with myeloma include? [3]
- Well-defined lytic lesions (described as looking “punched-out”) e.g. Raindrop skull
- Diffuse osteopenia
- Abnormal fractures
What is the diagnostic criteria for MM? [3]
State the investigational technqiues that can be used for each of the above
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
What are the major and minor criteria for diagnosis of MM?
How many do you need of each? [1]
Describe the four stages to MM tx [4]
- induction therapy
- autologous stem cell transplantation (ASCT)
- maintenance therapy
- managing relapse or refractory disease.
Describe the four stages to MM tx [4]:
- induction therapy
- autologous stem cell transplantation (ASCT)
- maintenance therapy
- managing relapse or refractory disease.
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,
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.
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.
Which complications need to be managed in MM? [5]
Describe the treatment used to manage these complications [+]
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.
Describe the typical presentation of MM bone disease [2]
Bone pain
Fractures of vertebral bodies - related to osteolytic bone lesions
Describe the specific managment for myeloma bone disease [5]
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
What is used as a prognostic tool for myeloma? [1]
Beta-2 microglobulin levels
What are the different stages for MM prognosis that are based off beta-2 microglobulin levels [3]
Stage I: median survival 62 months
Stage II: median survival 44 months
Stage III: median survival of 29 months
How do you differentiate between benign paraproteinaemia and myeloma? [1]
MGUS:
- absence of myeloma-related organ or tissue damage (predominantly renal, skeletal or bone marrow impairment).
Patients are often elderly and in good health.
Describe overall treatment plan for myelomas [3]
