Multiple Myeloma Flashcards
Symptoms of multiple myeloma
bone pain, fatigue, weakness, weight loss
hypercalcemia,
elevated proteins
renal dysfunction
platelet dysfunction
infections
amyloidosis
lab findings of MM
anemia,
elevated Cr,
hypercalcemia,
monoclonal protein on serum or urine protein electrophoresis.
Urine dipstick protein/quantitative protein analysis discordance.
Plasma cells >10% in bone marrow
elevated ESR
will see low anion gap because of high albumin levels.
what do you see on imaging with MM
Lytic lesions on CT, PET/CT scan, MRI,
on XR osteoporosis, compression fractures or pathological fractures
urine total protein Cr ratio benefits:
looks all protein in urine’ not just albumin which dipstick only detects. Can account for Bence Jone’s proteins or paraproteins leaked in to urine
presence of this lab worsens prognosis for MM
Cr elevation >1.5 worsens prognosis
focal segmental glomerulonephrosis has what on labs:
proteinuria and nephrotic syndrome. no protein gap No hypercalcemia either.
sarcoidosis can have
hyperabsorptive hypercalcemia and granulomatous interstitial nephritis and hypercalciuria that leads to kidney stones and obstructive uropathy.
Does not have differences in dipstick and quantitative methods of proteinuria.
diagnostic criteria for MM
monoclonal protein in serum or urine
>10% clonal plasma cells in bone marrow or soft tissue bone plasmacytoma
end organ damage with CRAB
what does CRAB stand for in MM?
calcium elevation renal insufficiency anemia bone pain (lytic lesions)
diagnostic tests for MM sensitivity are:
serum protein electrophoresis (for M spike) detects and quantifies a presence of a heavy chain immunoglobulin (Ig something) (light Kappa>lambda)
Serum immunofixation increases sensitivity >90% for detecting the M spike in addition to the determining the subtype of immunoglobulin that created the M spike (IgG usually) and if it’s a monoclonal or polyclonal M spike.
Kappa/lambda light chains - detect and quantify presence of light chains and their ratio. >4 is abnormal.
Can multiple myeloma patients not have an M spike on serum electrophoresis?
yes. UP to 20% can have only a urine light chain and they represent 3% of multiple myeloma cases
Three tests for MM
SPEP or UPEP - if there’s an immunoglobulin M protein present
serum immunofixation - tells you the subtype of immunoglobulin and if it’s monoclonal or polyclonal
kappa lambda light chain ratio - detects and quantifies the presence of light chains
what if there’s a negative serum and urine studies but presence of >10 plasma cells and CRAB
pt has non secretory MM MM without secretion of protein in serum
Side effect of lenalidomide
increased risk for VTE
what is MGUS?
monocolonal gammopathy of undetermined significance (MGUS)
definition of MGUS
M protein <3 g/dl and <10% of bone marrow clonal cells and no end organ damage.
asymptomatic and smouldering myeloma definition:
>10% bone marrow clonal cells WITHOUT evidence of organ damage. or by >60% bone marrow clonal cells
multiple myeloma is defined as:
>10% bone marrow clonal cells with evidence of end organ damage or by >60% bone marrow clonal cells
even if you suspect MGUS must get this test to rule in or out definitively
bone marrow biopsy
Next step after diagnosis of MM
needs a skeletal survey
plain radiographs of bones (skeletal survey) are needed to look for lytic lesions (don’t use bone scans- can detect increased osteoblast activity)
light chain amyloidosis manifestations
large tongue restrictive cardiomyopathy and nephrotic syndrome
MGUS surveillance
after established diagnosis of MGUS need to get follow up every 3 to 6 months
then yearly if stable.
when to get skeletal survey
need to get it in monoclonal gammopathies to exclude lytic bone lesions and severe osteopenia
Comparison of MM and spectrum of MGUS, smoldering and Waldenstrom
there is a risk for M type MGUS to progress to Waldenstrom Macroglobulinemia.
Treatment of Multiple Myeloma is based on
is pt a transplant candidate?
transplant candidate: needs a high dose chemotherapy + autologous stem cell transplant
Non transplant candidates : systemic chemotherapy of melphalan, thalidomide, lenalidomide.
Do we use flow cytometry for diagnosis of MM?
no, it can be used with getting positive markers (CD138 and CD38) but this does not define or diagnose MM.
Prognosis of multiple myeloma?
median survival ranges from 15 to 60 months
not great
Treatment of smoldering multiple myeloma
M component >3 g/dl and bone marrow biopsy with plasma cell percentage >10% (between 10-60%)
no crab criteria
doesn’t require treatment unless there’s signs of progression of smoldering MM.
Should know that transition to MM can be abrupt so if there’s any changes need to be reevaluated
follow with serum electrophoresis after 3 months and in 6 months.
what does a normal plasma cell do?
it produces clones that produce immunoglobulins of different classes and specificity giving the characteristic polyclonal spike on protein electrophoresis.
part of humoral immunity that is stimulated by infection or inflammation.
a plasma cell dyscrasia is a
monoclonal gammopathies that have clonal expansion of palsma cell or lymphoplasmacytic cells which cause a monoclonal spike on SPEP.
Can be a complete immunoglobulin with a heavy chain (IgG, IgA, IgM, IgE) complexed with a light chain (kappa or lambda) or free light chains without heavy chain component.
what does SPEP and UPEP detect
what does free light chains detect?
what do serum and urine immunofixations detect?
SPEP or UPEP can be a good screening test and to identify and quantify presence of M spike (presence of heavy chain immunoglobulin). Cannot identify subtype of immunoglobulin
serum free light chains to detect and quantify if there’s unbound (not attached to heavy chain) free light chains
serum and urine immunofixation helps to differentiate the SUBTYPE of immunoglobulin and differentiate a monoclonal spike from a polyclonal spike
what is a polyclonal spike in immunofixation tell you?
what does an increased free light chain amount but normal ratio mean?
polyclonal spike seen on immunofixation = infections, inflammatory processes and chronic liver dx. No further hematological evaluation despite if there’s an M spike on SPEP
Increased free light chains but normal ratio= clonal plasma cell expansion in the setting of infection or inflammation.
work up for suspected multiple myeloma
CBC with diff
serum chemistries
Cr
calcium
albuin levels
beta microglobulin
SPEP and UPEP
serum and urine immunofixation
serum free light chain tests
quantitative immunogloublins
plain radiographs of bones (skeletal survey) are needed to look for lytic lesions (don’t use bone scans- can detect increased osteoblast activity)
select pts can get PET and MRI
smoldering MM is evaluated every
3 to 6 months for risk of progression.
monoclonal gammopathy of renal significance is:
MGUS with significant kidney dx
treat like myeloma like therapy to prevent irreversible kidney injury?
complications associated with multiple myeloma?
infection - from leukopenia and hypogammaglobulinemia
increased risk for respiratory infections
vertebral fractures and pathological fractures from lytic lesions and from hypercalcemia
cast nephropathy and AKI
pain
side effects of lenalidomide and pomalidomide
VTE
some pts are considered for VTE prophylaxis
Treatment of MM?
evaluate if candidate for autologous hematopoietic stem cell transplant.
NOT curative but improves progression free and overal survival.
Those who are elegible for transplant get induction chemotherapy then get transplant are observed.
induction chemotherapy: immunomodulatory (lenalidomide or thalidomide), proteasome inhibitors (bortezomib), dexamethasone and alkalyating agents (cyclophosphamide)
then lenalidomide maintenance after transplant.
Tx for MM is not curative. Will have relapse at some point
Bortezomib and thalidomide side effects
peripheral neuropathy
bortezomib - has risk for herpes zoster reactivation so needs prophylaxis with acyclovir.
what can help prevent risk for skeletal fractures in MM?
bisphosphonates.
watch for hypocalcemia and jaw necrosis.
HCT (stem cell transplant) eligible?
no if they have:
CHF
confined to bed
>77 yrs
cirrhosis
IF not stem cell transplant eligible then treatment is:
do VRd induction: bortezomib + lenalidomide + low dose dexamethasone
then lenalidomide maintenance.
bortezomib prophylaxis to prevent what?
bortezomib - has risk for herpes zoster reactivation so needs prophylaxis with acyclovir.
Difference between MM and MGUS is with
low dose CT skeletal survey not XR
