Myeloma Flashcards
What is multiple myeloma and how can it be identified histologically?
Patchy disease of tumour of plasma cells in bone marrow
Large number of plasma cells with eccentric nuclei
What is the most common disease associated with multiple myeloma? What are the implications of this disease?
Bone disease
Causes pain and increase mortality and morbidity
Indicates treatment needs to commence
What acts a cancer marker for multiple myeloma? What causes the levels of this marker to increase or decrease?
M- protein (myeloma protein)
Increase= relapse Decrease= treatment
How many types of intact Ig are produced in myeloma? What can be produced instead of intake Ig?
1 type= monoclonal Ig
Kappa and lambda light chains can be produced instead of paraprotein (intact protein)
What are the symptoms of active myeloma? When should you consider multiple myeloma with patients?
C= hypercalcaemia R= renal impairment A= anaemia + fatigue B= Bone pain + destruction i.e. fracture and cord compression I= infection
When patient continually presenting with back pain along with other symptoms
What is the diagnostic criteria for multiple myeloma?
M-protein >30g/L
+/- bone marrow plasma cells >10% (Norm= 5%)
Symptoms of end organ damage (CRABI)
What is MGUS? How does it differ to multiple myeloma?
Monoclonal gammopathy of uncertain significance
Pre-malignant condition= no symptoms (no end organ damage)
Monoclonal protein <30g/L
Bone marrow damage <10%
Why does bone disease arise in multiple myeloma? What kind of lesions does it result in?
Altered metabolism in MM prevents new bone from forming
Lytic lesion
I.e. diagnostic and differentiates from other forms of bone cancer which produce sclerosis lesions
Why is renal failure associated with multiple myeloma?
MAIN= Light chain component from Ig precipitates into tubules
Leads to cast neuropathy= myeloma kidney
Addition reasons:
- dehydration
- infection
- hypercalacaemia
- uric acid
- amyloid
- acute tubular necrosis
Why is hyperviscosity associated with multiple myeloma? What are the symptoms associated with hyperviscosity?
High Ig concentration
Headaches Confusion Visual disturbance Bleeding Ischaemic event Angina
What can cause amyloid sardoisis in multiple myeloma?
Light chains can be deposited as EC protein
What is plasmacytoma and how does it relate to multiple myeloma?
Localise deposition of plasma cells in bony or soft tissue
Risk factor for developing multiple myeloma
What are the main complications of raised Ig levels in multiple myeloma?
Renal failure
Hyperviscosity
How would you diagnose myeloma? What are other clinical signs to look out for?
- Blood test= excess of monoclonal Ig i.e. M-protein
NOTE: need to check for light chains (present in 15% of cases) - Protein electrophoresis i.e. separation of proteins with peak for Ig
- Bone marrow aspirate i.e. looking for plasma cells >5%
- Skeletal survey i.e. core whole body MRI
- FBC
- Blood chemistry i.e. looking for hypercalcaemia
- B2 microglobulin
Clinical signs:
- anaemia
- renal impairment
- total protein raise
- hypercalcaemia
- immunoparesis (suppression of other Ig)
Why is it hard to treat multiple myeloma?
Disease evolves over time
Patients have heterogenous response to treatment
Non-curable
Can enter plateau phase after treatment which can last for years
What genetic change is associated with multiple myeloma?
Translocations into 14q32
Why is the BM microenvironment important for myeloma progression?
- Protects the myeloma and encourages drug resistance
- Immunosuppressive molecules alter the stroma to promote growth
- Stromal cells increase expression of OPGL (osteoprotegrin ligand) and down regulate OPG == increased osteoclast stimulation= increased bone resorption
What are examples of supportive management in multiple myeloma?
Pain= individual to the patient
Anaemia= erythropoietin injections or blood transfusions
Infection= IV antibiotics
Bone pain= radiotherapy
Hypercalcaemia= IV fluids/ Pamidronate IB (bisphosphonate) i.e. switches off osteoclasts activity
Depression/anxiety= support groups
Bone disease= Analgesia/radiotherapy/chemo/orthopaedic surgery/ Bisphosponate
What are the 2 medical emergencies which can arise with multiple myeloma? How are they managed?
- Renal failure
- Aggressive hydration
- Stop nephrotoxic drugs i.e. NSAIDs
- Treat myeloma with dexamethosone - Cord compression due to posterior movement damaged vertebrae
- Surgery if unstable
- Radiotherapy if stable
- Treat myeloma
What is anti-myeloma treatment and when is it indicated?
Drugs specifically targeting myeloma cells
Symptomatic patients i.e. those with end organ damage
What are the anti-myeloma drugs available as part of intensive treatment? State the mechanisms and adverse effects.
Bortezomid (Velcade)
Blocks proteasome to cause cell death via build up of toxins
A.E= nausea/diarrhoea/fatigue/headaches/constipation/thrombocytopenia/ peripheral neuropathy/ neutropenia
Thalidomide
Stimulates increased NK and TC activity and modifies cytokines and acts as anti-angiogenic
Lenalidomide (Revilimid)
A.E.= myelosuppression and increased risk of thrombosis
What are the current drug treatment regimens for multiple myeloma?
VTD (velcade-thalidomide-dexamethasone)
VCD (velcade- cyclophosphamide-dexamethasone)
CTD (cyclophospamide-thalidomide-dexamethason)
What is the process of stem cell transplant for multiple myeloma?
Myeloma needs to be remission and controlled before transplantation
Stimulate stem cells to enter blood via GCSF and mild chemo
Collect on apheresis machine (centrifuge)
How does autologous peripheral blood stem cell transplant differ from other stem cell transplant?
What are the associated risks?
Stronger dose of chemo required to save from BM failure
Risks due to lacking white cells for 2-3 weeks:
- infection
- mucousitis
- fatigue
- anorexia
When is non-intensive treatment used for multiple myeloma?
What are the current regimens?
When patient not suitable for BM transplant i.e. majority of time
VMP (Velcade-melphalan-predniolone)
VCD (Velcade-cyclophosphamide-dexamethasone)
Or Alkylating agent-steroid-thalidomide
Eg MPT or CTD
What is a common complication with myeloma therapy and how is it managed?
Thrombosis
Anticoagulents therapy
I.e. Full dose warfarin (INR 2-3) or Asparin + full dose LMWH
How is Daratumumab used to treat myeloma?
Monoclonal Ab
Has better response in patients w/o previous hx of treatment (decreased risk of resistance)
Increased efficacy when in combo with other drugs
