Onco 1: Leukemia Flashcards
(61 cards)
1
Q
Anthracycline (class) ADR
A
- myelosuppression - drop blood count (kind of what we want it to do in treatment of leukemia)
- cardiac tox (life time dose to reduce risk of HF)
2
Q
cytarabine HiDAC ADR
hidac - high dose
A
- neurotox (cerebellar/motor area)-> neuro check prior to each dose
- conjunctivitis -> give dexamethasoe eye drops Q6H (or artificial tears Q1-2H) during and 3 days after HiDAC is compelte
- hand-foot syndrome (palmar rash)
3
Q
gemtuzumab ozogamicin ADR
A
- infusion related reaction -> premedicate with APAP, benadryl, methylprednisolone
- hepatotox: including fatal veno-occlusive disease
4
Q
azacitidine ADR
HMA
A
- constipation -> standing bowel regimen
- low-moderate emetogenicity -> pre medicate with ondansetron
5
Q
secondary AML
A
- ## secondary prior to chemo; much poorer outcomes
- anthracyclines
- alkylators
- topoisomerase inhibitors
6
Q
cytogenetics and AML
A
- predict ability to obtain remission with induction chemo, risk of relapse, and overall survival
- looks at chromosomal abnormalities in leukemia cells
7
Q
FMS-like tyrosine kinase (FLT3) mutation
AML
A
- targetable proliferative mutation
- has subtypes
- internal tadem duplication (ITD) - worse prognosis
- tyrosine kinase domain (TKD)
8
Q
isocitrate dehydrogenase (IDH) mutation
AML
A
IDH 1 and 2 are targetable mutations
9
Q
risk stratification in AML
A
- based on cytogenetics and mutatiosn
- idnetifies prognosis relative to relapse (risk of relapse after remission)
- poor and intermediate risk likely to relapse without stem cell transplant
10
Q
“clogged pipe”
AML
A
- hypercellular bone marrow: immature cells otugrow all other cells - crowding out -> cytopenia
- goal of AML treatment is hypocelllular to allow for normal hematopoeisis
11
Q
hyperleukocytosis
A
- onco emergency
- can present with hyperviscosity syndrome (“blood sludging”)
- can present with
- SOB
- vision change
- stroke
- retinal hemorrhage
- resp failure
- cardiac ischemia
- renal failure
12
Q
management of hyperleukocytosis
A
hydroxyurea: “count control”, it suppresses it until we can acutely treat - use until pt clinally stable and ready to start chemo
dose is whatever works tbh
13
Q
hydroxyurea MOA
A
ribonucleotide reductase inhibitor
14
Q
hydroxyurea ADR
A
- N/V/D
- TLS
- long term tox: unlikely to occur in the treatment of hyperleukcytosis dt short duration
- cutaneous vasculitic ulcerations
- mucositis
- alopecia
- hyperpigmentation
15
Q
AML: who qualifies for aggressive induction chemo
A
- <60
- > 60 with NO signficiant comorbidites
- aggressvie dsiease
- canditiate for transplant
16
Q
aggressive inductio chemo treatment pathway for AML
A
- cytarabine 7 days+ anthracyline 3 days (daunorubicin or idarubacin)
- bone marrow biopsy at day 14
- if pt leukemia free at bone biopsy: wait for count recovery and re-biopsy for documentation of complete remission; if NOT, reinduction or salvage therapy
- after complete remission: consolidation and consderation for bone marrow transplant
in step 1 can use lipossomal daunorubicin/cytarbine if pt qualifies
17
Q
what is considered leukemia free at day 14 in AML?
A
bone biopsy
- 5-10% blasts
- hypocellular
- < 10-20% cells
18
Q
what is cosidered complete remission in AML?
A
- <5% blasts
- ANC > 1000
- plts > 100,000
19
Q
what to do if pt fails reinduciton or salvage therapy in AML?
A
switch over to supportive care/comfort measures
20
Q
treatment for pts who did NOT qualify for aggressive induction chem in AML
A
- low-intensity chemo
- azacitidine + venetoclax
- if pt has IDH1: ivosidenib+venetoclax
- if pt qualifies: gemtuzumab ozogamicin
- if pt progresses, switch to supportive care/comfort measures
pts who go down this route do NOT receive curative treatment
21
Q
venetoclax DDI
A
azole antifungals -> dose reduce
22
Q
relapse AML treatment
A
- venetoclax if pt has NOT received it in the past
- targeted relapse treatment
- gilteritinib: FLT - ITD or TKD
- ivosidenib: IDH1
- enasidenib: IDH2
23
Q
AML consolidation treatment
A
-
pts with favorable outcomes:high dose cytarabine (HiDAC)
- give with growth factor (do NOT give growth facotrs to plts with active AML) - pt who have intermediate/high risk: can get stem cell trasplant
24
Q
growth factor ADR
A
bone pain (treat with claritin)
25
AML inductio chemo: 7+3
- day 1-7: chemo admin (ADR: N/V, GI, fatigue)
- day 8-24: cell count nadir, plt transfusion, recovery (ADR: fatigue, fever, infection, high RBC)
- day 25+: complete cell count recovery - dcc from hospital once ANC > 500 and pt no longer transfusion dependent
26
AML additive agents to induction 7+3
- **FLT3-ITD: quizartinib** o days 8-21 of induciton and 6-19 of consolidation
- **FLT3-TKD (and technically ITD): midostaurin** BID with food on days 8-21 of induction and consolidation
- **favorable/intermediate cytogenetics: gemtuzumab ozogamicin** on days 1, 4, 7 of induction and day 1 of consoldiaiton
27
quizartinib ADR
cardiac (QT prolongation)
28
midostaurin ADR
smell so bad pts throw up
29
when to use liposomal daunorubicin/cytarabine instead of 7+3 in aggressive AML induction therapy
in pts with t-AML or AML with myelodysplatic related changes (AML-MRC)
| better outcomes than 7+3 in secondary AML
30
mutation of interest in CML
9;22 translocation (philadelphia chromosome)
## Footnote
test for prior to treatment, if pt doesn't have, it's likely not CML
31
CML presentation
- mostly asymp
- splenomegaly
- WBC > 25 x 10^9
32
chronic phase CML
- <10% blasts
- treatment: TKI
- treatment goal: delayed progression, eradicate Ph chromosome
33
accelerated phase CML
- blasts 10-19%
- treatment: TKI (at probs a higher dose than chronic phase)
- treatment goal: control WBC, go back to chronic phase and avoid progression
34
blast phase CML
- blasts > 20%
- treatment: treat like AML and slap on a TKI
- treatment goal: suvivie iduciton, bridge to allogenic stem cell transplant
35
TKI class ADR
- myelosuppresision
- transaminitis
- electrolyte changes
36
TKI agents by generation
- 1st gen: imatinib
- 2nd gen: dasatinib, nilotiib
- 3rd: bosatinib, polatinib
- other; asciminib (binds ot Myristoyl pocket instead of ATP pocket)
37
which TKIs need to be dose adjusted in hepatic impairment
- imitinib
- nilotinib
- bosutinib
- ponatinib
38
whcih TKIs need to be dose adjusted in renal impairment
imitanib
39
T315I mutation
- the "gatekeeping mutation"
- mutation that prevents most TKIs from working
- treat the CML with ascimiib (preferred) or ponatinib
40
CML treatment monitoring
molecular response: look at transcript level of fusion protein (which leads ot proliferation) -> quantifiy amount of that protein in your blood
41
CML treatment: BCR-ABL goal
- @ 3 months: BCR-ABL < 10%
- @ 6 months: < 1%
- @ 12 months: < 0.1%
## Footnote
if not meeting goal, look into reaosns why
42
picking a TKI
low/intermediate risk: dasatinib preferred dt tolerability
- can also just do
- bosutinib
- nilotinib
- imatinib (not preferred in intermedate)
43
CML remssion treatmetn
can actually dc a TKI if pt is completely in remssion and meets other strict requirements
44
imatinib off target effect
inhibits
- PDGFR
- c-KIT
45
imatinib ADR
fluid build up: peripheral edema
46
imatinib: DDI
CYP 3A4 substrate and nihibitor
47
dasatinib off target effects
inhibits
- PDGFR
- c-KIT
- Src family kinases
| results in edema
48
dasatinib ADR
fluid build up: pleural effusions
49
dasatinib DDI
CYP3A4 substrate
50
dasatinib admi
needs acidic environment to absorb -> no H2RA or PPI
51
nilotinib ADR
cardio (Qt porlongation, arrhythmias)
52
nilotinib admin
BID on ann empty stomach
53
nilotinib DDI
- CYP3A4 substrate and inhibitor
- CYP 2C8, 2C9, 2D6 action
54
bosutinib off target effects
ihibits
- Src kinases
- Lyn kiases
- Hck kinases
## Footnote
in terms of on-target effects has activity against a lot of mutations that early drugs don't, however, does NOT cover T315I or V299L
55
bosutinib ADR
diarrhea for first 2 weeks
56
bosutinib DDI
CYP3A4 substrate
57
poatinib off targe effects
inhibits
- VEGFR
- PDGFR
- Src kinases
- FGFR
- FLT3
- RTK
- TIE2
## Footnote
active agaist all mutaitons
58
ponatinib ADR
- vascular occlusion - ppx asa
- HF
- hepatotox
| it's very poorly tolerated
58
ponatinib DDI
CYP 3A4 substrate
59
indication for asciminib
- if pt has T315I mutaiton or
- if pt has received 2+ TKi in past
| CML
60
asciminib admi
empty stomach
