Ha - Multiple Myeloma Flashcards
what is MM
ca of plasma cells of bone marrow
describe the MM plasma cells
terminally differentiated
monoclonal IgG secreting
what do MM plasma cells make
monoclonal IgG or IgA
excess kappa or lamda serum free light chains
bence jones proteins
what is waldenstroms
lymphoplastic lymphoma
MM is the ___ most common cancer and ___ most common blood cancer
19th
2nd
median age of MM
67
incidence increases with age
MM is higher in what sex / race ?
higher in males / black
RFs of MM
obesity
genetics - black, sporadic family myeloma
premalignant conditions
when is MM preceded by a pre malignant condition
ALWAYS
what premalignant condition preceeds MM
MGUS - monoclonal gammopathy of uncertain significance
what is MGUS
presence of monoclonal IgG in the blood
age preference of MGUS
incidence increases with age
1-3.5% elderly population
what % of MGUS progress to MM each year
1%
what does MGUS IgG/A type progress to?
MGUS IgM type?
IgG/A –> myeloma
IgM –> lymphoma
what does MGUS increase your risk of, other than MM
osteoporosis
thrombosis
bacterial infection
criteria for diagnosing MGUS
serum M < 30g/L
BM clonal cells >10%
no lytic bone lesions / myeloma related tissue damage / B cell proliferative disease
how is the risk of MGUS progression stratified
Mayo criteria
RFs for MGUS
non IgG M spike
M spike >15g/L
abnormal serum free light chain ratio
describe how number of RFs relates to risk of progression to MM
0 RFs = 2%
1 RF = 10%
2 RFs = 18%
3 RFs = 27%
does everyone that has MGUS get MM?
NO - most people are fine and never get myeloma
diagnostic criteria for smouldering myeloma
serum IgG or IgA >30g/L
BM clonal plasma cells 10-60%
no myeloma events
is mouldering myeloma malignant
no - premalignant
RFs for developing myeloma from smouldering myeloma
BM myeloma cells >20%
M spike >20g/L
serum FLC ratio >20
what is the Tx for myeloma
no treatment
only sx mx to prevent relapse
list primary events that can cause myeloma
hyperdiploidy
IGH rearrangements - Chr14q32
which is the most common primary cause of myeloma
hyperdiploidy 60%
list chr14q32 IGH rearrangments that can cause myeloma
t(11,14)
t(4,14)
t(14,16)
list secondary events that can cause myeloma
KRAS, NRAS
t(8,14)
1q gain / deletion
deletion of 17p (TP53)
13-/del 13q
how does myeloma affect the bone
anaemia
bone destruction
immunosuppression and infections
angiogenesis
why does myeloma cause bone destruction
myelome plasma cells stimulate osteoclast interaction
sx / signs of myeloma
CRAB
- high Ca
- renal disease
- anaemia
- bone disease - fractures, lytic lesions, pain
diagnostic criteria of myeloma
> 10% plasma cells in BM
plasmacytoma and 1+ CRAB Sx
diagnostic criteria of myeloma
> 10% plasma cells in BM
plasmacytoma and 1+ CRAB Sx
list myeloma defining events
BM plasma cells >60%
involved:uninvolved FLC ratio >100
1+ focal lesion in MRI >5mm
what % of myeloma patients have bone disease
80%
list bone disease Sx of myeloma
proximal skeleton issues
osteolytic not osteoblastic (salt and pepper skull)
osteopenia
high ca
Ix for myeloma bone issues & why
CT / PET MRI
- can see BM cellularity and active/Tx effect on disease
list 2 medical emergencies that can occur as a consequence of MM
cord compression
high calcium
Ix for ?cord compression due to MM
MRI
Ig and FLC studies
+/- biopsy
Mx of ?cord compression due to MM
dexamethasone
radiotherapy
surgery (rare)
Sx of high calcium due to MM
drowsy
constipated
tired
muscle weakness
AKI
Tx of high calcium due to MM
IV fluids
steroids
zolendronic acid
define kidney disease in MM
serum creatanine >177umol/L
or
eGFR <40ml/min
what % of MM patients have AKI at presentation
20-50%
what causes kidney problems in MM
cast nephropathy due to high serum FLC and bence jones proteinuria
consequences of kidney disease in MM
high mortality - 12% early death
increases hospital stays
infections
reduced drug suitability as many drugs renally excreted
Mx of kidney disease in MM
bortezomib Tx to remove FLC
why do MM patients get infections
reduced serum normal IgGs - immunoparesis
myeloid and T cell impairment
chemotherapy reduces immunity
which infections in particular affect MM patients
gram + and viruses - esp HSV
Ix for MM
Ig studies
- serum / urine protein electrophoresis
- 24hr BJP collection
BM biopsy and aspiration
FISH analysis
flow cytometry immuniphenotyping
Name a risk stratification score of myeloma
R-ISS
what does R-ISS use to stage MM
microglobulin
albumin
genetic abnormalities
high LDH
pathogenesis of amyloidosis
misfolded light chains aggregate into amyloid fibrils in target organs
what stain is used to visualise amyloidosis
congo red
what effects does amyloidosis have on organs
nephrotic syndrome
unexplained HF
sensory neuropathy
abnormal LFTs
macroglosia
what % of amyloidosis patients have nephrotic syndrome
70%
what is MGRS
monoclonal gammaopathy of renal significance
- Ig LCs damage nephron
what is the key MM histopath marker
CD138
Drug Tx of MM
belantamab
ventoclax
BiTE
CAR-T cells
prognosis of MM
usually >10 year survival
new drug Tx of MM
cereblon E3 ligase modulators
proteasome inhibitors
name 3 proteasome inhibitors
bortezomib
carfilozomib
ixazomib
name the 1st monoclonal AB for MM
daratumab
what does daratumab target
CD38 - a marker in normal plasma cells
describe transplant process for eligible MM patients
induction –> SCT –> consolidation –> maintenance
Tx for transplant ineligible MM patients
dartumumad + lenolimide + dex
OR
bortezomib + cyclophosphamide + dex
OR
dara - borte - cyclo - pred
side effects of CAR T cells
cytokine release syndrome
neurotoxicity
prolonged cytopenias and infections
what is BiTE
bispecific AB
- one part binds CD3 of T cell, other recognises TSA of tumour cell therefore bringing the 2 together to encourage T cell destruction of cancer cell
