Multiple Myeloma Flashcards
Median age of diagnosis MM
70 years
T/F MM is more common in African Americans compared to Caucasians
True
MM occurs in which cells?
plasma cells –> Ig producing cells
MGUS (monoclonal gammopathy of unknown significance) is what?
pre-myeloma disease
1% per year progression to MM
What do MM cells secrete?
cytokines/chemokines
IL-6, VEGF, RANKL, etc
______ are activated and ______ are inactivated in MM causing -_________
osteoclasts
osteoblasts
severe bone disease
CRAB acronym is for what?
What does it stand for?
Incidence of each?
MM C = hypercalcemia (25%) R = renal failure (50%) A = anemia (70%) B = bone lesions (80%)
Symptoms of MM
bone pain
fatigue
recurrent infection
T/F about 20% of MM lack light chain and secrete heavy chain
False
20% lack heavy chain
Secrete light chain
What is detected on SPEP in 80-90% of MM when coupled with immunofixation?
m protein
Diagnosis of MM requires
plasma cells in marrow or plasmacytoma
+
M protein in serum/urine
What all is used in diagnosis of MM?
lytic bone lesion
urine electrophoresis
Low risk smoltering MM treatment
Observation or
Lenalidomide + low dose dexamethasone
High risk smoltering MM treatment
Observation or
Lenalidomide + low dose dexamethasone
Ultra high risk smoltering MM treatment
Lenalidomide + low dose dexamethasone
Characteristics of high risk smoltering MM
free light chain ratio of at least 8 and cytogenetics
Anemia in MM
fatigue, weakness, SOB
Renal dysfunction in MM
rising SCr due to tubular obstruction with light chains, IgG and IgA
Hypercalcemia in MM
due to bone lesions
dehydration, CNS, etc
Bacterial infections in MM
decreased normal IgG and decreased lymphocyte function
Osteolytic lesions in MM
Local secretion of IL-6, IL-1, RANK-L leads to increase osteoclast activity and decreased osteoblast activity
Neurologic symptoms in MM
cord compression
hyeprviscosity syndrome
Partial response (PR) in MM
>/= 50% decrease in M protein >/= 90% decrease in 24 hour urine light chain
Very good partial response (VgPR) in MM
Negative SPEP
Serum and urine M protein detected on immunofixation
Complete remission (CR) in MM
negative SPEP and negative urine immunofixation
no soft tissue plasmacytomas
<5% plasma cell in bone marrow
Stringent CR (sCR) in MM
meets all criteria for CR and normal free light chain ratio (FLC)
Immunomodulatory drugs (IMiDs) in MM
- Thalidomide
- Lenalidomide
- Pomalidomide
T/F Lenalidomide has a higher %CR in MM than thalidomide
true
T/F lenalidomide is not teratogenetic?
false!
none in rabbits
yes in monkeys
REMS program
ADE of thalidomide
- REMS
- VTE
- sedation
- neuropathy
- toxic epidermal necrolysis
ADE of lenalidomide
- REMS
- VTE
- myelosuppression
- rash
- fatigue
ADE of pomalidomide
similar to lenalidomide
T/F combination chemotherapy is still use to treat MM
False!
no longer used due to better tolerated and more active alternatives
T/F high dose dexamethasone is NOT used in MM treatment anymore
True!
Not well tolerated in older patients
Less active than combinations
T/F low doses of oral melphalan + prednisone is used to treat MM
true
But seldom used due to well tolerated more active newer agents
- cheap, oral, well tolerated
Which of the IMiDs has more data for use in relapsed/refractory patients?
Pomalidomide
T/F thalidomide is an analog of lenalidomide
False!
Lenalidomide is an analog of thalidomide
Which proteasome inhibitors are used in MM?
Bortezomib
Carfilzomib
Ixazomib
What is the main treatment regimen for MM?
IMiDs + low dose dexamethasone
ADE of bortezomib
Myelosuppression
Neuropathy
Immunosuppression
ADE of carfilzomib
myelosuppression liver cardiac neuropathy pulmonary
ADE of ixazomib
myelosuppression
neuropathy
What is the first oral proteasome inhibitor used in MM?
Ixazomib
Induction therapy for MM
ASCT
ASCT non-candidates
frail low risk patients - use 2 drug regimen (Rd)
frail high risk patients - use 3 drug regimen (VRD)
How many cycles of induction do ASCT candidates use?
4 cycles
VRd
KRd
MM chemotherapy IMiD combinations
- Melphalan or CTX + IMiDs or proteasome inhibitors
- Liposomal doxorubicin + bortezomib
- Bendamustine + lenalidomide + bortezomib
Novel agents in MM
Panobinostat
Elotuzumab
Daratumumab
MOA of panobinostat
Pan histone deacetylase inhibitor
MOA of elotuzumab
antibody which targets SLAM F7
MOA of daratumumab
antibody which targets CD38
When are the novel agents used in MM?
salvage therapy
What is panobinostat used with?
carfilzomib and panobinostat + bortezomib + dexamethasone
What is elotuzumab used with?
bortezomib + dexamethasone
What is daratumumab used with?
bortezomib or lenalidomide + dexamethasone
ADE of panobinostat
myelosuppression
diarrhea
neuropathy
ADE of elotuzumab
myelosuppression
infusion reactions
ADE of daratumumab
myelosuppression
infusion reactions
T/F two AutoHSCT transplants (tandem) may be used in MM patients
true!
in patients who receive suboptimal response with first transplant
t/f low dose melphalan is used to prepare patients for autoHSCt
false
High dose
T/F autoHSCT cannot be used at the time of relapse
false
Stem cell collection in MM for autoHSCT
collect sufficient cells to do multiple transplants BEFORE receiving HD melphalan
Allogeneic transplant in MM
full intensity transplant –> high early mortality
reduced intensity transplant –> high relapse rates
T/F allogeneic transplant is first line in MM
false!
no major role in treating MM
Should triple therapy or double therapy be used in MM?
triple therapy has improved progression free survival
Who would you use Melphalan + prednisone in MM?
older patients with symptoms
How long is induction in MM before autoHSCT?
4 months!
When would you consider someone relapsed/refractory MM?
if progression occurs > 6 months after end of primary induction
T/F in relapsed/refractory MM you can repeat the same induction therapies
false!
switch to a different drug1
T/F relapsed MM patients have a higher risk of VTE than newly diagnosed
false
other way around
Which drug class doesn’t add to VTE risk in MM?
proteasome inhibitors
VTE in MM is usually due to which drugs?
IMIDs or dexamethasone
MM patient with underlying risk of VTE or high risk drug combo what do you give?
LMW heparin
MM patient without underlying risks for VTE and receiving lenalidomide + low dose dexamethasone what do you give?
ASA
Bone disease in MM treatment
Bisphosphonates
reassess in 2 years –> risk of ONJ and renal toxicity
