CML/CLL Flashcards
1
Q
Average age of diagnosis in CML
A
64
2
Q
Average age of diagnosis of CLL
A
70
3
Q
T/F there are more NEW cases of CML than CLL
A
False
CLL > CML
4
Q
T/F there are more deaths from CML than CLL
A
False
CLL > CML
5
Q
What is the most common leukemia in the US?
A
CLL
6
Q
T/F CLL is idiopathic?
A
True
7
Q
T/F you usually know the cause of CML
A
False
Usually do not know
- likely increased by environmental exposure which damage chromosomes
8
Q
Pathophysiology of CML
A
- reciprocal translocation b/t chromo 9 & 22
- shorted arm of chromo 22 = Ph chromo
- creates fusion gene bcr-abl
- creates TK
- constitutively active
9
Q
What blast % is found in chronic phase of CML?
A
<10% in peripheral blood or bone marrow
10
Q
What blast % is found in accelerated phase of CML?
A
10-29% in peripheral blood and bone marrow
11
Q
What blast % is found in blast crisis in CML?
A
>30% in peripheral blood and bone marrow
12
Q
How long does chronic phase of CML last?
What is it associated with?
A
can last for years
Associated with funcitonal myeloblasts
13
Q
How long does the accelerated phase of CML last?
What is it associated with?
A
Lasts weeks
Associated with therapy resistance and disease progression
14
Q
How long can you live in blast crisis in CML?
A
Die in days to weeks
15
Q
Without treatment, CML disease progresses within how many years?
A
~5 years
16
Q
What can be used to quickly lower WBC in CML?
A
Hydroxyurea
17
Q
What can be used if WBCs are dangerously high in CML?
A
leukophoresis
18
Q
What drug can decrease WBC the slwoest in CML?
A
TKIs
19
Q
T/F hydroxyurea can help slow disease progression in CML
A
False
TKIs help slow disease progression
20
Q
Which TKI is the ONLY one that works for T3151 mutation in CML?
A
Ponatinib
21
Q
Imatinib binds the inactive/active confimation of bcr-abl?
A
inactive
22
Q
Nilotinib binds the inactive/active confimation of bcr-abl?
A
inactive
23
Q
Dasatinib binds the inactive/active confimation of bcr-abl?
A
active
24
Q
Bosutinib binds the inactive/active confimation of bcr-abl?
A
both!
25
What is a complete hematologic response (CHR)?
normalization of peripheral blood counts
26
What is a major cytogenetic response (MCR)?
= 35% Ph+ cells on metaphase in bone marrow
27
What is major molecular remission (MMR)?
PCR shows 3 log decline in bcr-abl from baseline
28
What is complete molecular remission (CMR)?
PCR shows 4-5 log decline in BCR-abl from baseline
29
MMR =
109 cells
30
T/F IFN-a is used in CML
False
used to be, but not anymore!
- dose related and required life-long tx
31
Imatinib is 1st gen/2nd gen
Dasatinib is 1st gen/2nd gen
Ima: 1st
Das: 2nd
32
What is IFNa usually combined with for CML treatment?
ARA-C
33
T/F IFNa + ARA C is better than imatinib in CML
False!
Ima \> IFNa + ARA C
34
Toxicities of Imatinib
- hepatoxic
- hematologic tox
**- fluid retention**
- muscle pain/cramps
GI symptoms
35
What to tell patient on imatinib
Take with food and large glass of water
DDI with warfarin: increase INR; consider therapy modification
36
T/F imatinib is more potent than dasatinib
false
das 300x \> ima
37
T/F dasatinib has no difference in overall or progression free survival compared to imatinib
true
- increased response rates though
38
Dasatinib has an increased rates of what toxicities compared to imatinib
pleural effusions
QT prolongation
39
Toxicities of dasatinib
pleural effusions
QT prolongation
PAH: potentially fatal!
40
Imatinib DDIs
3A4, 2Ds and pgp inhibitor
41
Dasatinib DDIs
pH dependent: decreased abs with PPI and H2 antag
3A4, PGP inhibitor
42
Which has a deeper response: imatinib or dasatinib?
Dasatinib!
4-5 log decline (CMR)
43
T/F nilotinib has a higher rate of response to imatinib
true!
but no difference in overall or progression free survival!
44
T/F imatinib has higher rates of cardiovascualr events than nilotinib
false!
Nilo \> ima
45
Boxed warning for nilotinib
QT prolongation
46
Nilotinib has lower rates of what ADE compared to imatinib
fluid retention
GI symptoms
47
Unique ADE of nilotinib
may cause metabolic effects
48
T/F Nilotinib has an equal molecular response compared to imatinib
false
greater response!
4 log decline (MMR)
49
4 log decline
MMR
50
4-5 log decline
CMR
51
T/F dose doesn't affect toxicities with nilotinib
false!
dose related toxicity
52
Unique ADE of bosutinib
Diaraha and skin toxicity
53
T/F bosutinib is more likely to cause QT prolongation compared to nilotinib
false!
Nil \> bos
54
Which TKI in CML is multi-targeted?
ponatinib
55
Toxicities of bosutinib
thromboembolism
liver tox
HF
vascular tox
56
T/F it is not a good idea to get patients off of TKIs in CML
False!
good idea!
57
When can you think about stopping TKIs in CML?
- after DEEP molecular response \>/= 2 years
- patient consent
- discussed risk/benefits
- have chronic phase
- no previous history of accelerated or blast phase
- on TKI for 3 years
58
When would you restart TKI therapy in CML?
after recurrence (~6 months)
59
T/F almost all patients will re-establish molecular response when TKI restarted in CML
true
60
What is a risk of discontinuing TKIs?
TKI withdrawal
61
How long must you be on TKI therapy in CML before discontinuing?
at least 3 years
62
How long should you have a stable molecular response in CML before discontinuing TKIs?
How many tests?
How long apart are the tests?
2 years
4 tests
3 months apart
63
How often do you monitor after discontinuing TKIs?
- monthly x 1 year
- Q6 weeks thereafter
64
Prompt resumption of TKI within ____ weeks of loss of MMR
4
65
What to tell patient on dosatinib
take with or without meals
Avoid H2 antagonists/PPIS
66
What to tell patient on niloinib
avoid food 2 hours before or 1 hour after dose
avoid drugs that prolong QTc
67
What to tell patient on bosutinib
take with food
avoid PPIs (decrease abs)
68
What to tell patient on ponatinib
take with or without food
69
Which TKI in CML can also be used in ALL?
ponatinib
70
Which TKI should you avoid in CML with lung disease?
dasatinib
71
What non-TKI drug has activity against T3151 mutation in CML?
What is the MOA?
omacetaxine
protein synthesis inhibitor
72
Major toxicity of omacetaxine
bone marrow suppression
73
When would you use omacetaxine?
Intoelrant or unresponse to 2 prior TKI therapies in CML and ponatinib
74
What is the only proven curative therapy in CML?
allogenic stem cell transplant
75
Pathophysiology of CLL
Neoplastic clone of CD5+ B lymphocytes
loss of normal apoptosis
76
What mutations are common in CLL and can be used as biomarkers?
TP53
del(17p)
77
S/S of CLL
fatigue
fever (w/o infection)
night sweats
weight loss
78
Physical exam of CLL
lymphadenopathy
splenomegaly
hepatomegaly
79
Peripheral blood labs in CLL
lymphocytosis
autoimmune hemolytic anemia
hyepr/hypoagammaglobulinemia
thrombocytopenia
80
Bone marrow labs in CLL
hypercellular
increase mature lymphocytes
increased megakaryocytes
81
Tx: CLL w/o del/mutation
\< 65 yo w/o signif co-morbidities
FCR regimen
bendamustine + CD20 mab
Ibruitnib
82
Tx: CLL w/o del/mutation
\> 65 yo or younger patients with co-morbidities or frail patients
Obinutuzumab + chlorambucil
Ibrutinib
Bendamustine + CD20 mab
Rituximab + chlorambucil
Ofatumumab + chlorambucil
83
Tx: CLL w/o del/mutation
Post 1st line maintence therapy
lenalidomide
84
Tx: CLL w/o del/mutation
Relapsed/refractory
ibrutinib
venetoclax + rituximab
Duvelisib
Idelalisib + rituximab
85
Tx: CLL WITH del/mutation
Ibrutinib
post 1st line: lenalidomide
86
What to tell patient on lenalidomide
Risk of DVT/PE: prophylaxis with ASA 81 mg
teratogen: contraception for males and females
87
Main ADE of ibrutinib
severe diarrhea --\> hydration, loperamide
myelosuppression
88
When is venetoclax used in CLL?
relasped or refractory CLL
89
Major ADE of venetoclax (according to McGuire)
TLS
severe diarrhea
myelosuppression
90
Which drugs in CLL can have infusion related reactions and need premed?
Rituximab: APAP, benadryl
Ofatumumab: same + steroid
Obinutuzumab: same + steroid
91
Is infection more common in CLL or CML?
CLL
92
What vaccines to give CLL patients
No live!
annual flu
pneumococcal Q5 years
93
What antibiotics to give to prevent infection in CLL patients
Herpes: acyclovir
PJP: SMP/TMX
HBV: entecavir if HBsAg+
94
What is a complete cytogenetic remission (CCyR)?
0% Ph+ cells on metaphse in the bone marrow
