Onco 2: M&Ms - multiple myeloma (not the candy) Flashcards
multiple myeloma
- plasma cell disorder: B cells create dysfunctional Ab (Mprotein/monoclonal proten); mass production of those dysfunctional Ab
- SPEP and UPEP (serum/urine protein electrophoresis) can determine what dysfunctional Ab is being secreted (IgG, IgA, FLC, IgD, IgM)
FLC: only light chain of AB is being mass produced
risk factors for multiple myeloma
- black
- old
- male
- radiation
- chemicals (firefighter, farmer)
- genetics: MGUS, immediate family hx
- obesity
- immune suppression: solid organ transplant on immunsuppressive therapy, HIV, AIDS
MGUS
- M protein < 3
- bone marrow plasma cells < 10%
- about 1% of pts per year with this progress to multiple myeloma
smoldering multiple myeloma
- M protein > 3
- bone marrow plasma cells > 10%
- Bence Jones potein (light chains) in urine
- about 10% of pts per year with this progress to multiple myeloma
multiple myeloma vs smoldering MM and MGUS
- end organ damage (SLM CRAB)
- biopsy proven bony or extramedullary plasmaytoma
- M protein > 3 (also in smoldering)
- bone plasma cells > 10% (also in smoldering)
SLM CRAB
- S:ixty - 60% bone marrow plasma cells or more
- L: ight chains - ratio of uninolved (at least 10) to uninvolved is > 100
- M:RI - > 1 foca lesion that is > 5mm
- C:a - > 1 above ULN or > 11
- R:enal - CrCl 40 or SCr > 2 (poor prognosis)
- A:nemia - Hgb > 2 below LLN or < 10
- B:one - 1+ osteolytic lesion on imaging
myeloma and bone disease
myeloma cells infiltrate bone marrow
- increased produciton of cytokines -> damages bone, drives myeloma growth
- increased osteoclast acitivty -> upregulatio of RANKL and RANK and decreased osteoprotegerin productoin
consequences of multiple myeloma bone disease
- lytic lesions and fractures
- anemia dt plasma cell invasion of bone marrow
- hyper Ca because bone resorption releases Ca
multiple myeloma induced renal impairment causes
- hyper Ca
- myeloma cast nephropahty: precipitaiton of light chains in distal tubule
- ostruction
- inflammation
- fibrosis - renal impairment -> decreased erythropoietin
multiple myeloma supporitve care
- bisphosphonates or denosumab for 2 yrs (longer as clincally appropriate)
- if anemia: blood transfusions or Epo
- infection
- acyclovir for everyone (ppx HZV)
- levofloxacin for everyone - reduces febrile episodes and death - if diarrhea: loperamide
- avoid NSAIDs
denosumab preferred if pt has bad renal funciton
how long to treat multiple myeloma
indefintely until pt dies or wants to swtich to comfort care
no cure
treatment pricniples for multiple myeloma
- quick disease control while preserving bone marrow function (quicker pt gets to minimal residual disease, the less likely to relapse/flare)
- triplet or quadruplet therapy
- determine transplant eligibilty
- supportive care
bisphosphonate admin in multiple myeloma
- as supportive care for 2 years (longer if clincally appropriate)
- no dose adjsutment needed when treating hyperCa
- zoledronic acid preferred in hypercalcemia in multiple myeloam
triplet v quadruplet therapy for multiple myeloma
- triplet aka RVd: Revlimib (lealidomide) + Velcade (bortezumab) + dexamethasone
- quadruplet: daratumumab + RVd
pts who may benefit from quadruplet: newly diagnosed transplant eligible patients - quadruplet regimen leads to improved stringent complete response (sCR) and minimal resiudal disease negativty (MRD)
transplant in multiple myeloma
- autologous (cells from self) transplant after unduction chemo
- goal is to eventually do 2 transplants
consdierations for multiple myeloma transplant
- age
- renal, hepatic, cardiac, functon
- performances status
- caregiver support
daratumumab MOA
anti CD38 1gG1 - kappa human mAb
daratumumab admin
- SQ preferred over IV dt duration time
- premedicate
- steroid: dexamethasone or methylprednisolone
- APAP
- antihistamine: benadrl, hydroxyzine
- montelukast with first dose - post medicate: methylprednisolone 2D after each dose of first cycle
dt infusion reaction
Quad: Daratumumab-RVd
daratumumab ADR
- infusion reaction: pre and post medicate
- HZV and/or Hep B reactivation
- lab interference
- SPEP/SIFE
- Ab detection test
- anti human globulin crossmatches
- indirect antiglobulin tests
bortezumab MOA
protesasome inhibitor, inhibits S20 subuit of the proteasome -> apoptosis
bortuzumab ADR
- HZV reactivation
- thrombocytopenia
- peripheral neuropathy (esp with IV, so we prefer SQ)
ADR for class, though the neuropahty is worse for bort
possible agents to help with bortezumab induced peripheral neurpathy
- vit B complex
- duloxetine
- GABA analog
other drugs in same class as bortezumab and their ADR
- carafilzomib: cardiac and pulm tox (requires ECHO), though least neuropathic
- ixazomib: GI tox -> take PO on empty stomach
if borth neuropathy too much, can switch to bortezumab
lenalidomide MOA
immunomodulatory, anti-angiogenic
- upregulation of apopotoic factors
- decreased anti-apoptotic factors
- decreased production of cytokines
- enhanced T cell and NK cell proliferation and activity
Immunomodulatory drug (IMiD)
lenalidomide ADR
- birth defets - REMS
- hematologic tox and thrombocytopenia -> need anticoag
- somolence
- inreased risk of secondary malignancy
- rash, skin tox
- diarrhea
think thalidomide
lenalidomide REMS
- 2 preggers test prior to start and then Qmo - after paperwork is filed, pt has 7 days from negative preggers test to fill
- need one highly effective for of birth cotrol (IUD, COC, tubal litagation, or partner vasectomy) + other birth control (condom, diaphragm, or cervical cap)
- surveys Qmo if child bearing potential (otherwise Q6mo) to confirmm adherence to above
anticoag ppx for lenalidomide pts
- use existing tpx anticoag and maybe add asa
- if no existsing coag: lovenox 40QDor dose-reduced eliquis
- if pt is NOT at high risk for VTE, can reduce to baby asa after parital response (50% reduciton in M protein)
dexamethasone MOA in multiple myeloma
suppression of inflammatory cytokines and trasncrption protens -> induce cell cucle arrest
other steroids cna be use too
dexamethasone ADR
- insomnia
- mood change
- increased appetite
- GI upset/reflux
- hyperglycemia
- HTN
- wt gain
- edema
multiple myeloma relapse therapy
- based on prior therpay and ADR
- 4th line: CAR-T or BiTE (bispecific T-cell engagers)
if using BiTE, use one that targets a tumor antigen and an immune related molecule
BiTE options for multiple myleoma and their targets
- talquetamab: GPRC5D
- elranatamab: BCMA
- teclistamab: BCMA
talquetamab ADR
NOT teclistsamab
- cytokine release syndrome
- ICANS
- cytopeias
- skin and nail tox
- taste change
- wt loss
elranatab ADR
- CRS
- ICANS
- cytopenias
teclistamab ADR
NOT talquetamab
- CRS
- ICANS
- cytopeias
BiTE therapy admin
- step up dosing to ensure tolerability
- high enough dose needs to be done in hospital
- pts with hx of CRS or ICANS should also get dose in hospital
BiTE REMS
ensures provider education/training and proper pt couneling
pts should also have a wallet card identifiying CRS and ICANS ADR
CRS: cytokine release syndrome
increased cytokines dt T cell activaton -> inflammatory response
CRS grade 1
fever
CRS grade 2
- fever
- hypotension
- mild hypoxia
CRS grade 3
- fever
- hypotension - one vasopressor
- hypoxia - high flow O2 needed
CRS grade 4
- fever
- hypoentsion - on multiple vasopressors
- hypoxia - on CPAP, BiPAP or mecahcal ventilaion
ICANS
- type of neurotox
- dt disruption of BBB annd increased cytokines in CSF
ICANS grade 1
- ICE score 7-9
- awake spontaneously
ICANS grade 2
- ICE score 3-6
- awake to voice
ICANS grade 3
- ICE score 0-2
- awake to physical stimuli
- clinical or focal seizure which resolves rapidly
- focal/local edema on imagg
ICANS grade 4
- ICE score 0
- unarousable, stupor, coma
- life-threatening, prolonged seizure, reptitive seizure with no retur to baeline
- deep focal motor weakness
management of ICANS
- antiseizure med if appropriate
- steroids
- supportive care
