Multiple Myeloma Flashcards
what is multiple myeloma?
malignancy of plasma cells
what two places can mm be measured in?
plasma or urine
what are the genetic factors implicated with mm?
- familial clusters of mm
- multiple genetic mutations (immunoglobulin gene rearrangements)
mm may be preceded by?
MGUS and smoldering mm
describe MGUS
- presence of monoclonal immunoglobulin in blood (≤3 g/dL)
- <10% clonal plasma cells in bone marrow
- absence of clinical manifestations of MM (e.g. end-organ damage)
- conversion rate of MGUS to MM is 1%/year
describe smoldering mm
- advanced premalignant stage
- monoclonal immunoglobulin in blood (≥3 g/dL)
- 10%-60% plasma cells in bone marrow
- no clinical manifestations of mm
what is a malignant plasma cell involved in unregulated production of a monoclonal antibody?
m-protein
mm cells supported by supportive bone marrow microenvironment that promotes further expansion of myeloma clones including:
IL-6
VEGF
IGF-1
NK-kB
is mm typically symptomatic or asymptomatic?
symptomatic
what are signs and symptoms of mm?
bone pain
fatigue
infection
neurologic symptoms
polyuria
n/v
what are labs associated with mm?
elevated m-protein
elevated SCr
hypercalcemia
low Hb
low albumin
elevated B2-microglobulin
elevated C-reactive protein
what is the main cytogenetic associated with mm?
Del (17p)
what is the acronym associated with mm?
CRAB:
hypercalcemia
renal insufficiency
anemia
bone lesions
for the staging and prognosis of mm what does the revised international staging system include?
serum B2-microglobulin
albumin
LDH
high-risk chromosomal abnormalities
describe stage I values of mm
serum β2 -microglobulin <3.5 mcg/mL
serum albumin ≥3.5 g/dL
no high-risk cytogenetics
normal LDH
describe stage II values of mm
not stage I or III
describe stage III values of mm
sSerum β2 -microglobulin ≥5.5 mcg/mL
high-risk cytogenetics [t(4;14), t(14;16), del(17p)] or
Elevated LDH
for newly diagnosed patients who can tolerate chemotherapy and are transplant eligible patients primary therapy may be followed by?
transplant and
maintenance therapy
initiating treatment depends on what?
if the patient is experiencing symptoms
is early conventional treatment benefical in patients with MGUS or smoldering mm?
no
but some new agents investigated in high-risk smoldering mm may improve survival and delay progression
what does the initial therapy for mm include?
dexamethasone
IMiDs
proteasome inhibitors
what is the frequently used regimen that is considered the standard of care for initial mm therapy?
bortezomib
lenalidomide
dexamethasone
initial therapy depends on whether the patient is what two things?
- symptomatic
- candidate for autologous HSCT
what are the eligibility factors for HSCT?
age
renal function
performance status
comorbidites
If candidates for autologous HSCT they
generally receive 4-6 months of therapy before hematopoietic stem cell collection and there needs to be enough stem cells for how many transplants?
2
single agent maintenance therapy consists of what drugs?
lenlidomide
bortezomib
high-dose dexamethasone is associated with what 3 things?
- higher risk of infection
- CNS toxicity
- use caution in elderly patients
what are the 3 IMiDs?
thalidomide
lenalidomide
pomalidomide
what are the 2 MOA’s of IMiDs?
- decrease production of cytokines and growth factors
- may also inhibit NF-kB
what are the major side effects/toxicities associated with IMiDs?
- VTE
- severe birth defects and embryo-fetal death (REMS program)
what are the 3 proteasome inhibitors?
bortezomib (IV)
carflizomib (IV)
ixazomib (PO)
what is the main MOA of proteasome inhibitors?
inhibit proteasome and NF-kB activation
what are the main side effects/toxicities associated with bortezomib?
- fatigue
- GI
- neuropathy (less neurotoxicity when administered subQ)
what are the main side effects/toxicities associated with carfilzomib?
- peripheral neuropathy (less than bortezomib)
- CV
- pulmonary
what are the main side effects/toxicities associated with ixazomib?
- myelosuppression
- rash
- neuropathy
- infections including herpes zoster
- GI
- cardiac (less than carflizomib)
what is the monoclonal antibody that targets CD38?
daratumumab
what is the chimeric IgG- derived monoclonal antibody that also targets CD38?
isatuximab-irfc
what is the monoclonal antibody directed against SLAMF7?
elotuzumab
what is the antibody-drug conjugate targeting B cell maturation (BCMA)?
belantamab mafodotin
what is the REMS program associated with belantamab mafodotin?
ophthalmic exam prior to each dose, patients should use lubricating eye drops while on therapy
what is an oral inhibitor of histone deacetylase enzymes?
panobinostat
what is the side effects/toxicities associated with panobinostat?
- GI
- QTc prolongation
- myelosuppression
- infection
- hepatoxicity
what is the first in new class of drugs that inhibits nuclear export of tumor suppressor proteins (TSPs) and Exportin 1 (XPO1)?
selinexor
what is the side effects/toxicities associated with selinexor?
- myelosuppression
- infection
- GI
- neurotoxicity
in 2021, FDA-approvedwhat drug for the treatment of relapsed or refractory MM?
idecabtagene vicleucel
what is the lenalidomide/bortezomib/dexamethasone regimen?
- lenalidomide PO daily x 14 days
- bortezomib subcutaneously days 1, 4, 8, and 11
- dexamethasone PO daily days 1, 8, and 15Repeat q 21 days
what are the bone modifying therapies?
- Bisphosphonates (zoledronic acid, pamidronate)
- Denosumab
what are the side effects/toxicities associated with the bone modifiying therapies?
osteonecrosis of the jaw (ONJ)
does zoledronic acid require dose adjustments for renal impairment?
yes, not recommended if CrCl <30 mL/min
does pamidronate require dose adjustments for renal impairment?
consider a reduced initial dose if renal impairment
does denosumab require dose adjustments for renal impairment?
no
what does the monoclonal antibody denosumab direct towards?
RANK-L
The combination regimen for the initial treatment of multiple myeloma includes which of the following?
a) Dasatinib, proteosome inhibitor, and immunomodulatory agent
b) Dexamethasone, proteosome inhibitor, and immunomodulatory agent
c) Dasatinib, proteosome inhibitor and cisplatin
d) Doxorubicin, paclitaxel, proteosome inhibitor, and immunomodulatory agent
B
Multiple myeloma is a malignancy of which of the following?
a) Of T cells only
c) Of Plasma cells (e.g. immunoglobulin-producing B lymphocytes)
c) Characterized by clonal proliferation and accumulation of a monoclonal immunoglobulin secreted from the plasma cell that can be measured in the plasma or urine
d) A and B are correct
e) B and C are correct
E
Bortezomib can be used for the treatment of multiple myeloma because it is a proteosome inhibitor which leads to inhibition of which of the following?
a) NF-kB
b) BCR-ABL
c) mTOR
d) HER-2
A
