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PHM 703: Crit Care/Heme/Onc > Onco 2: M&Ms - multiple myeloma (not the candy) > Flashcards

Onco 2: M&Ms - multiple myeloma (not the candy) Flashcards

1
Q

multiple myeloma

A
  • 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

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2
Q

risk factors for multiple myeloma

A
  • black
  • old
  • male
  • radiation
  • chemicals (firefighter, farmer)
  • genetics: MGUS, immediate family hx
  • obesity
  • immune suppression: solid organ transplant on immunsuppressive therapy, HIV, AIDS
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3
Q

MGUS

A
  • M protein < 3
  • bone marrow plasma cells < 10%
  • about 1% of pts per year with this progress to multiple myeloma
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4
Q

smoldering multiple myeloma

A
  • 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
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5
Q

multiple myeloma vs smoldering MM and MGUS

A
  • end organ damage (SLM CRAB)
  • biopsy proven bony or extramedullary plasmaytoma

  • M protein > 3 (also in smoldering)
  • bone plasma cells > 10% (also in smoldering)
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6
Q

SLM CRAB

A
  • 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
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7
Q

myeloma and bone disease

A

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

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8
Q

consequences of multiple myeloma bone disease

A
  • lytic lesions and fractures
  • anemia dt plasma cell invasion of bone marrow
  • hyper Ca because bone resorption releases Ca
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9
Q

multiple myeloma induced renal impairment causes

A
  • hyper Ca
  • myeloma cast nephropahty: precipitaiton of light chains in distal tubule
    - ostruction
    - inflammation
    - fibrosis
  • renal impairment -> decreased erythropoietin
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10
Q

multiple myeloma supporitve care

A
  • 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

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11
Q

how long to treat multiple myeloma

A

indefintely until pt dies or wants to swtich to comfort care

no cure

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12
Q

treatment pricniples for multiple myeloma

A
  • 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
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13
Q

bisphosphonate admin in multiple myeloma

A
  • 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
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14
Q

triplet v quadruplet therapy for multiple myeloma

A
  • 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)

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15
Q

transplant in multiple myeloma

A
  • autologous (cells from self) transplant after unduction chemo
  • goal is to eventually do 2 transplants
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16
Q

consdierations for multiple myeloma transplant

A
  • age
  • renal, hepatic, cardiac, functon
  • performances status
  • caregiver support
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17
Q

daratumumab MOA

A

anti CD38 1gG1 - kappa human mAb

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18
Q

daratumumab admin

A
  • 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

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19
Q

daratumumab ADR

A
  • 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
20
Q

bortezumab MOA

A

protesasome inhibitor, inhibits S20 subuit of the proteasome -> apoptosis

21
Q

bortuzumab ADR

A
  • HZV reactivation
  • thrombocytopenia
  • peripheral neuropathy (esp with IV, so we prefer SQ)

ADR for class, though the neuropahty is worse for bort

22
Q

possible agents to help with bortezumab induced peripheral neurpathy

A
  • vit B complex
  • duloxetine
  • GABA analog
23
Q

other drugs in same class as bortezumab and their ADR

A
  • 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

24
Q

lenalidomide MOA

A

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)

25
Q

lenalidomide ADR

A
  • birth defets - REMS
  • hematologic tox and thrombocytopenia -> need anticoag
  • somolence
  • inreased risk of secondary malignancy
  • rash, skin tox
  • diarrhea

think thalidomide

26
Q

lenalidomide REMS

A
  • 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
27
Q

anticoag ppx for lenalidomide pts

A
  • 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)
28
Q

dexamethasone MOA in multiple myeloma

A

suppression of inflammatory cytokines and trasncrption protens -> induce cell cucle arrest

other steroids cna be use too

29
Q

dexamethasone ADR

A
  • insomnia
  • mood change
  • increased appetite
  • GI upset/reflux
  • hyperglycemia
  • HTN
  • wt gain
  • edema
30
Q

multiple myeloma relapse therapy

A
  • 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

31
Q

BiTE options for multiple myleoma and their targets

A
  • talquetamab: GPRC5D
  • elranatamab: BCMA
  • teclistamab: BCMA
32
Q

talquetamab ADR

NOT teclistsamab

A
  • cytokine release syndrome
  • ICANS
  • cytopeias
  • skin and nail tox
  • taste change
  • wt loss
33
Q

elranatab ADR

A
  • CRS
  • ICANS
  • cytopenias
34
Q

teclistamab ADR

NOT talquetamab

A
  • CRS
  • ICANS
  • cytopeias
35
Q

BiTE therapy admin

A
  • 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
36
Q

BiTE REMS

A

ensures provider education/training and proper pt couneling

pts should also have a wallet card identifiying CRS and ICANS ADR

37
Q

CRS: cytokine release syndrome

A

increased cytokines dt T cell activaton -> inflammatory response

38
Q

CRS grade 1

A

fever

39
Q

CRS grade 2

A
  • fever
  • hypotension
  • mild hypoxia
40
Q

CRS grade 3

A
  • fever
  • hypotension - one vasopressor
  • hypoxia - high flow O2 needed
41
Q

CRS grade 4

A
  • fever
  • hypoentsion - on multiple vasopressors
  • hypoxia - on CPAP, BiPAP or mecahcal ventilaion
42
Q

ICANS

A
  • type of neurotox
  • dt disruption of BBB annd increased cytokines in CSF
43
Q

ICANS grade 1

A
  • ICE score 7-9
  • awake spontaneously
44
Q

ICANS grade 2

A
  • ICE score 3-6
  • awake to voice
45
Q

ICANS grade 3

A
  • ICE score 0-2
  • awake to physical stimuli
  • clinical or focal seizure which resolves rapidly
  • focal/local edema on imagg
46
Q

ICANS grade 4

A
  • ICE score 0
  • unarousable, stupor, coma
  • life-threatening, prolonged seizure, reptitive seizure with no retur to baeline
  • deep focal motor weakness
47
Q

management of ICANS

A
  • antiseizure med if appropriate
  • steroids
  • supportive care

PHM 703: Crit Care/Heme/Onc (16 decks)

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