myeloma Flashcards
what is multiple myeloma?
cancer of the plasma cells in the bone marrow (rarely occurs outside the bone marrow)
usually affects pelvis, spine, rib cage, skull, shoulders, hips
what is plasmacytoma?
a localised deposit of plasma cells which can be bony or in soft tissue. It may be associated with a small monoclonal protein
It is treated with radiotherapy but the chance of reccurance or develepment of multipl myeloma is high (greater if in bone rarther than soft tissue)
how do myeloma plasma cells differ from normal plasma cells?
like normal plasma cells they produce immunoglobulins, however they are clones of the same cell so they will all produce the same immunoglobulins. There may also be production of broken down bits of immunoglobulin such as lamda light chain or kappa light chain.
this means that specific immunoglobulin levels can be used as a marker of disease
outline the epidemiology of multiple myeloma
- increased in older populations
- increasing in prevelance as the population is ageing and less people are dying of other things
- increased in afro-carribean populations
- There is no single genetic abnormality that defines this disease. Huge number of different variations of translocations into 14q32 but there are also patients that have no translocation at all.
what are the features of multiple myeloma?
Vast majority of cases preceded by silent, asymptomatic precursor condition MGUS
MGUS - monoclonal gammopathy of uncertain significance. This is a benign disease which does not cause symptoms or damage A premalignant forerunner of myeloma caused by a tiny clone of plasma cells but monoclonal protein is still less than 30, bone marrow clonal cells is less than 10% and there is no evidence of organ damage.
This is common in the older population and over 90% of MGUS do not develop myeloma but 90% of myelomas have an MGUS stage
Active myeloma - CRABI
- C - hypercalcaemia
- R- renal impairment - due to light chain deposition in renal tubules which leads to cast nephropathy. - Dehydration, infection, hypercalcaemia, uric acid, amyloid and acute tubular necrosis can also play a factor in renal impairment and make it worse.
- A - anemia
- B - bone pain and destruction - fractures and compression
- I - infection
Because the symptoms are quite non specific the diagnosis may take a long time
how is multiple myeloma diagnosed?
- M-protein in serum higher than 30g/l - can do electrophoresis to determine this
- and/or bone marrow plasma cells more than 10%
- Related organ damage (CRABI) however there may be asymptomatic multiple myeloma with no organ damage
how is multiple myeloma staged?
Stage 1
- beta2-M less than 3.5mg/L and serum albumin more than 35g/L
Stage 2
- Neither stage one or three
Stage 3
- beta2-M more than 5.5mg/L
This staging is not that useful as there is a large variation in life expectancy so it is not a good prognostic marker
how is multiple myeloma monitored?
Core whole body MRI with no contrast - this will detect bone disease, has no radiation and will take 45 minutes. this should be done at the diagnosis and repeated when there is any new bone pain
Each time a patient comes to clinic monitor M protein, FBC and biochemistry
what are the complications of multiple myeloma?
bone disease
- this is the most common feature
- affects metabolism and switches off new bone formation
- affects quality of life and is a major cause of morbidity and mortality
- is an indication to start treatment
cord compression
pathological fracture
hyperviscosity
- confusion
- headache
- visual disturbance
- bleeding
- ischaemic event
- angina
amyloid disease
- nephrotic syndrome
- soft tisue involvement
- cardiac involvement
how do you describe the course of the disease in multiple myeloma?
It is a relapsing remitting disease. This means that it is not curable and there are periods when the disease is more quiet and others where it is more active
each relapse is more difficult to treat due to biology changes and drug resistance of tumour.
The plateau phase can last for months or years
how is multiple myeloma treated?
supportive management
- managing pain - analgenia
- managing anaemia - erythropoietin injections or blood transfusions
- managing depression or anxiety
- managing infections
- radiotherapy may be used to relieve bony pain but effects take a couple of weeks
- anticoagulants
- orthopaedics
treatment
- induction therapy if unsuitable for transplant or pre-transplant
- transplant - allogenic transplantation or PBSCT
- treatment of bone disease - radiotherapy, chemotherapy, surgery, physiotherapy, biphosphate (reduce risk of bony fractures and pain)
- treatment of renal impairment
antimyeloma treatment
this is only inidcated for symptomatic myeloma as non symptomatic patients will not benefit from early intervention
- transplant
- intensive treatment of combination of drugs:
VTD - velcade-thalidomide-dexamethasone
VRD- velcade-lenalidomide-dexamethasone
VCD - Velcade-cyclophosphamide-dexamethasone
RD - lenalidomide-dexamethasone
CTD - cyclophosphamide- thalidomide-dexamethasone
- less invasive drug treatments:
VMP - velcade-melphalan- prednisolone
VCD - velcade-cyclophosphamide-dexamethasone
Other combinations such as lenalidomide-dexamethasone, MPT, CTD
Other less intensive treatments are steroids alone (respond well but poor duration of response) or cyclophosphamide once a week alongside steroids.
treatment of any emergencies
what emergencies may arise in multiple myeloma and how are they managed?
renal failure
- Try to salvage renal function and avoid dialysis dependence as this has a poor prognosis
- Aggressive hydration
- Avoid nephrotoxic drugs
- Treat myeloma - dexamethasone initially
- Experimental drugs to remove light chains
hypercalcaemia
- IV fluid replacement - ideally 3 litres every 24 hours
- Then pamidronate or zoledronate
- Usually works but if not use dexamethasone once diagnosis is confirmed
- Treat myeloma as soon as possible
cord compression
- MRI scan
- Consult spinal surgeon - urgent surgery if instability
- If stable then radiotherapy
- Treat myeloma
hyper viscosity - caused by high levels of immunoglobulins
- Remove protein by plasma exchange
- Treat myeloma
infection - Typically bacterial
- Immunosuppressed patients who are usually not neutropenic
- Treat aggressively with IV antibiotics promptly
- Once myeloma controlled usually at less risk
what common drugs are used in myeloma and how do they work?
- Bortezomib (velcade) - targets the proteasome which usually acts as a recycling machine for the cell so if this is blocked the cell dies. Adverse effects include nausea, diarrhoea, fatigue, headache, constipation, thrombocytopenia, peripheral neuropathy, neutropenia
- Thalidomide - immunomodulatory drug. Don’t really understand how it works but we know it stimulates the immune system as well as having other effects. Cannot be used in pregnant women
- Lenalidomide - structurally similar to thalidomide but functionally different both qualitatively and quantitatively. Has less side effects and is therefore better tolerated. However, it is very expensive. May cause myelosuppression (anemia, neutropenia and thrombocytopenia) and thrombosis so pts must also be on anticoagulation.
- Daratumumab - first monoclonal antibody drug in myeloma. Has a large effect in patients who have not yet been treated. Works even better combined with other drugs such as lenalidomide.
what transplants are done for patients with multiple myeloma and what are the indications?
patients need to be in remission for a stem cell transplant to work so other therapies need to be used first.
Peripheral blood stem cell harvest stem cells can repopulate all blood cells
- Stimulate stem cells to leave bone marrow and come out into blood using white cell growth factor and sometimes mild chemotherapy
- Collect stem cells on apheresis machine which takes blood from one vein and centrifuges blood to take of stem cells and return blood to vein. Takes 4-6 hours and may need to do 1-3 days. Patient awake and it is a safe procedure done as an outpatient
- Store in freezer in liquid nitrogen or use immediately
Autologous peripheral blood stem cell transplant
- Allows us to give much stronger doses of chemotherapy by rescuing the patient with stem cells (patients own stem cells) - otherwise they would die of bone marrow failure. This is a serious procedure with a 3% mortality and Impatient for 3-4 weeks. The patient will have no white cells for 2-3 weeks so need IV antibiotics for infections. Also cause fatigue, anorexia, nausea, blood/platelet transfusions
- Not curative just improves survival
Allogeneic transplants
- using stem cells from another human who is a complete match.
- This has complications such as graft vs host disease and it is a dangerous procedure with a mortality rate of 11-18%. Most people will need immunosuppression long term which has its own risks.
how do we deal with the thrombotic effects of multiple myeloma therapy?
There is always thrombotic complications of myeloma therapy so most patients are on anticoagulants
- Low dose warfarin
- Full dose warfarin
- Aspirin and full dose LMWH
- Aspirin if there is an intermediate risk
- Epixiban
