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