myeloma Flashcards
what is myeloma a cancer of?
- malignancy of the B- cells - plasma cells
- bone marrow
- means the plasma cells can’t stop dividing
- causing very thick blood - leading to symptoms
- also don’t produce working Ig - result in large quantities of a single type of Ig - usually IgG / IgA
- instead they release paraprotein (M protein)
- can lead to failure of bone marrow, kidney disease and destruction of bone marrow
types of myeloma and compare them
MGUS → Very common, does NOT cause harm, only 1% per year risk of progression, no treatment needed.
Smouldering Myeloma → More advanced than MGUS but still NO symptoms; 20% risk per year of progression early on.
Symptomatic Myeloma → Causes organ damage, needs treatment.
what is Monoclonal gammopathy of undetermined significance (MGUS)
- production of paraprotein
- not cancer tho
- otherwise healthy
- 1% risk of progression to myeloma
- does not harm
Plasma cells in bone marrow: <10%
M protein in blood: <30 g/L
what is smouldering myeloma
Plasma cells in bone marrow: >10%
M protein in blood: >30 g/L
Still NO organ damage (ROTI)
high early risk of turning into multiple myeloma
still no treatment but monitor closely
whats symptomatic myeloma (multiple myeloma)
Meets MGUS/smouldering criteria, BUT also has ROTI (organ damage from the disease).
- hypercalcaemia
- Renal (kidney) failure
- Anemia
- Bone disease (lytic lesions, fractures)
- Amyloidosis (abnormal protein deposits in organs)
requires chemo / steroids / targetted therapy / bone stregnthening
key presentation
spikey old CRAB
spikey - paraprotein spike on serum plasmapheresis
old - >60yrs
CRAB
- hyperCALCAEMIA
- renal imparement
- anaemia + thrombocytopaenia Platelet count <150 × 10⁹/L
- bone disease
serum electropheresis?
- gel electropheresis
- seperation by electrical charge
- will show a band at the right of the gel
stats
- second most common haem cancer
- 70yrs
- survival ranges to few months to a few years
curable?
no - always relapsing and remitting
can plateu
investigations
- FBC - looks for anaemia
- erythrocyte sedimentation rate and plasma viscosity - will be high bc high paraprotein
- U&E + calcium - high Ca suggests bone involvement, high creatinine renal involvement and normal ALP
- LFT - high protein / globin fraction (low albumin - poor prognosis)
- serum / urine electrophoresis and serum light chains
- bone marrow biopsy - confirm >10% clonal plasma cells
- cross sectional imaging - bone lesions
- Urine dipstick - Bence Jones protein
briefly what is systemic AL amyloidosis
- disorder where misfolded light chains produced by abnormal plasma cells form amyloid deposits in tissues and organs
- leads to organ dysfunction and failure
- its not myeloma but symptoms v similar but myeloma doesnt cause organ dysfunction
Myeloma Bone Disease (MBD) and common sites
Almost 80% of patients have abnormalities in bone radiographs at diagnosis
Up to 90% of patients develop lytic lesions over the disease course
sites:
- vertabrae
- ribs
- skull
- shoulders
- pelvis
- long bones
why are bisphosphonates used?
- prevents and treats bone damage
- reduces bone pain
- lowers Ca levels
which bisphosphates are used?
Zoledronic acid (IV, most effective):
- Preferred due to strong anti-resorptive effect and survival benefit.
- 4mg Given monthly.
Pamidronate (IV):
- Alternative if kidney function is impaired.
- 90mg monthly
Clodronate (Oral) – Less effective, used in some cases.
- 1600mg daily
which myeloma patients shoukld recieve bisphosphonates?
All myeloma patients with ROTI should receive bisphosphonates
other monitoring and treatments
- check renal status and dental health with bisphosphates
- calcium 500mg daily
- ditamin D 400 IU daily
for 2 years
aims of treatment
obvs cannot treat so:
- reduce number of myeloma cells
- reduce symptoms and complications
- improve quality and legnth of life
Supportive treatment
Bisphosphonate to protect bones
Blood transfusions/ erythropoietin (EPO)
Anti-coagulation
Antibiotics as needed
Pain-killers as required
Radiotherapy
Kyphoplasty occasionally indicated
Psychological support
contrast blanket and bullet gene therapy?
blanket - not one singular gene - good in like polygenic disorders - cancers, neurodegenerative
bullet - precise monogenic disease - sickle cell
Types of anti-myeloma chemotherapies
Monoclonal antibodies – daratumumab, isatuximab (anti CD138)
Proteasome inhibitors – bortezomib (sc), carfilzomib (iv), ixazomib (po)
Immunomodulatory drugs – thalidomide and analogues lenalidomide (Revlimid) and pomalidomide
Corticosteroids – dexamethasone, prednisolone
Alkylating agents – cyclophosphamide, melphalan
T-cell engagers
CAR T-cell therapy
Quadruplet, triplet and doublet combinations commonly used
myoloma bone disease
- inc osteoclast
- inc growth factors
- inc anti-osteoblast
plasma cell level
> 10% plasma cells
What is renal failure caused by in multiple myeloma? (2)
- Hypercalcaemia -> calcium oxalase renal stones
- Immunoglobulin light chain deposition - Bence Jones protein in pee
Epidemiology of myeloma (5)
- Around 70 years old
- Afro-Carribeans
- Male
- Obesity
- 1% of cancers are myeloma
