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What are the 3 phases of chronic myelogenous leukemia (CML)? - ✔✔
- Chronic (increase in WBCs or Plts and splenomegaly, "stable phase" lasting 1-4 years)
- Accelerated phase ( ~ few months)
- Blast phase (transition to ACUTE leukemia)
What is the ONLY CURE for CML? - ✔✔Allogeneic HSCT (stem cell transplant)
When is AHSCT indicated? - ✔✔Blast crisis
accelerated phase
unresponsive or intolerant to TKIs
What is the purpose of TKIs in treating CML? - ✔✔To maintain patient in the chronic phase "stable phase"
Which 5 TKIs are approved for CML?
Hint: I DONT NEED BLOOD PUNK - ✔✔Imatinib
Dasatinib
Nilotinib
Bosutinib
Ponatinib
Imatinib (Gleevec) AEs - ✔✔Neutropenia, thrombocytopenia, edema, rash, CHF, cardiotoxicity
(T/F) imatinib is taken without regard to meals - ✔✔False, imatinib should be taken WITH FOOD!!
Which CYP enzymes does imatinib inhibit and which drug is contraindicated to be taken with imatinib? -
✔✔Imatinib inhibits CYP2C9 and CYP2D
AVOID WARFARIN w/ imatinib
What is dasatinib is indicated for? - ✔✔Treatment of newly diagnosed Ph+ chronic myeloid leukemia (CML) in chronic phase; treatment of chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib
Dasatinib (Sprycel) MOA - ✔✔small-molecule, DUAL inhibitor of ABL1 (binds to both active and inactive ABL1 confirmation) and SRC family kinase
Dasatinib is nearly active against all BCR-ABL1 mutations except for mutation.
Dasatinib associated AEs - ✔✔QTc prolongation, pleural effusions, reversible pulmonary arterial HTN, mild to moderate cytopenias, lymphocytosis
Nilotinib (Tasigna) MOA - ✔✔HIGHLY selective inhibitor of BCR-ABL1 TK (20-50 x more than imatinib resistant and 3-7 times more
Which two OTC drug classes should be AVOIDED when taking all TKIs except for imatinib? - ✔✔H2- blockers and PPIs
Which TKI used for CML has a black box warning (BBW) for QTc prolongation? - ✔✔Nilotinib has a BBW for QTc prolongation
What is Bosutinib indicated for/ MOA? - ✔✔CML Ph+ resistance or intolerance to prior TKI therapy.
MOA: Has activity to kinase domain mutations resistant to imatinib, dasatinib, and nilotinib.
(T/F) Bosutinib should be taken with food. - ✔✔True, Bosutinib should be taken WITH FOOD, while avoiding any H2-receptor blocker and PPI
will increase serum concentrations of TKIs and result in hematologic and liver toxicities or
increase other unwanted side effects. (CML) - ✔✔Voriconazole, posaconazole, isavuconazole, fl uconazole greater than 200mg
is the main reason CCyR and TKI failure - ✔✔non-compliance
First line therapy for CLL in patients older than 65 years old (first 3 therapies are the same for patients <
Venetoclax + Obinutuzumab
Aclaratunib
1st-line therapy for CLL in patients younger than 65 includes which therapy option that is excluded in
older patients - ✔✔Fludarabine, cyclophosphamide, rituximab (FCR)
BCL-2 inhibitor used to treat CLL - ✔✔Venetoclax
CD20 monoclonal antibody that has activity in fludarabine-refractory and alemtuzumab-refractory CLL -
✔✔Ofatumumab (Arzerra)
AEs: Hepatitis reactivation, PML, myelosuppression (given > 1 week)
Type II humanized CD20 IgG1 monoclonal antibody used to treat CLL in combination with venetoclax or
chlorambucil - ✔✔Obinutuzumab
Potent irreversible inhibitor of Bruton's tyrosine kinase that has drug interactions with CYP3A inducers
and inhibitors - ✔✔Ibrutinib (Imbruvica)
What 3 criteria are considered "favorable" regarding AML prognosis? - ✔✔Age < 60
Good risk cytogenetics
Low WBC @ diagnosis
Goals of therapy for complete response AML? - ✔✔1. No peripheral leukemic cells
- ANC > 1000
- Plts > 100,
- Bone marrow > 20% cellularity w/ maturation of all lineages
- Bone marrow < 5% blasts
What are the 2 phases of treatment for AML? - ✔✔Induction
COnsolidation
What drug regimens are used to treat AML during the induction phase? - ✔✔During the induction phase when treating AML, Cytarabine and an anthracycline (daunorubicin [DNR] or idarubicin) 7+ 3 ( 7 days of cytarabine and 3 days of an anthracycline)
Which agent do you add to induction AML therapy if FLT3 mutation is positive? - ✔✔Oral midostaurin
Anti-CD33 MAB - ✔✔gemtuzumab ozogamicin
_inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction; and intercalates at points of local uncoiling of the double helix (topoisomerase II
inhibition) - ✔✔Daunorubicin
What are the BBW for daunorubicin? - ✔✔Cardiotoxicity
Hepatic impairment
Myelosuppression
Infusion reactions
Assess and before administering cytarabine therapy. - ✔✔Renal function and age prior to therapy
Which AML treatment agent can cause conjunctivitis? How can it be treated? - ✔✔Cytarabine can cause conjunctivitis which can treated with steroid eye drops the first day and continuing 24hr post therapy.
What is the first-line treatment regimen for diffuse large B-cell lymphoma? - ✔✔RCHOP every 21 days
R= rituximab C=cyclophosphamide
H=hydroxydaurubicin aka doxorubicin
O= Oncovin aka vincristine
P=prednisone
What are the 4 electrolyte abnormalities associated with TLS? - ✔✔1. Hyperkalemia
- Hyperuricemia
- Hyperphosphatemia
- Hypocalcemia
What are risk factors for TLS based on tumor type? - ✔✔1. Burkitts lymphoma
- Lymphoblastic lymphoma
- ALL WBC > 100,
- diffuse large-cell lymphoma
- AML WBC >50,000, monoblastic
- tumors with high proliferative rates and rapid response to therapy hence lysing contents into blood faster
Which agents would you eliminate that may be contributing to TLS? - ✔✔K+ supplements
Phosphate supplements
K+-sparing diuretics
ACE-inhibitors
TZD diuretics
nephrotoxins
Hyperphosphotemia - ✔✔Oral phosphate binders with meals: Sevalamer, Lanthanum, Calcium acetate
When is hypocalcemia treated and with what agent? - ✔✔Only if symptomatic (tetany, arrhythmias)
Treated with Calcium gluconate 1-2 gm IV x 1 dose
Cornerstone of hypercalcemia treatment? - ✔✔Hydration +/- furosemide (avoid tzds diuretics)
