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Therapeutics P3 Spring > Leukemia > Flashcards

Leukemia Flashcards

1
Q

Signs and Sx of Leukemia

A

Anemia (fatigue, SOB)
Thrombocytopenia (bleed risk)
Neutropenia (ANC < 500, infection risk)
Tumor Lysis Syndrome
CNS involvement rare (somnolence, headaches, confusion)

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2
Q

Hyperleukocytosis definition

A

Elevated WBC
- >/= 100,00
- oncologic emergency
- hyperviscosity syndrome: blood sludging
- Sx: stupor, SOB, vision changes
- can lead to stroke, respiratory failure, cardiac ischemia, renal failure, retinal hemorrhage

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3
Q

Hyperleukocytosis management

A

Hydroxyurea
- used for count control
- used until clinically stable and ready for induction therapy

Leukopheresis

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4
Q

Hydroxyurea

A

Indication: Hyperleukocytosis
Dosing: physician/patient specific
ADE:
- N/V/D
- tumor lysis syndrome
- long term toxicities (cutaneous vasculitic ulcerations, mucositis, alopecia, hyperpigmentation

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5
Q

FMS-like-tyrosine kinase (FLT3) mutations

A

Internal Tandem Duplication (ITD)

Tyrosine Kinase Domain (TKD)

promotes proliferation and blocks differentiation
worse prognosis (both are bad ITD is worse than TKD tho)

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6
Q

Isocitrate dehydrogenase (IDH)

A

targetable mutation in AML

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7
Q

Criteria for high-intensity chemotherapy

A
  • most pts < 60
  • pts > 60 without significant comorbidities or end organ dysfunction
  • patients with aggressive disease (hyperleukocytosis, TLS at presentation)
  • pts who are candidates for allogenic stem cell transplant
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8
Q

7+3 Induction Chemo

A

7 days of cytarabine continuous infusion
3 days of anthracycline bolus
- daunorubicin OR
- idarubicin

ADE days 1-7:
- N/V, GI, fatigue

ADE days 8-24:
- fatigue, fever/infection, high RBC and platelet transfusion requirement

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9
Q

Additional Induction Regimens (AML)

A

Midostaurin
- for FLT3 + pts

Gemtuzumab Ozogamicin
- for favorable/intermediate cytogenetics

Liposomal Daunorubicin + Cytarabine
- for secondary (treatment induced) AML

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10
Q

Response criteria in AML

A

day 14 bone marrow testing:
- < 5-10% blasts

day 28 bone marrow testing for complete remission:
- <5% blasts AND
- ANC > 1000 AND
- Platelets > 100,000

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11
Q

AML Post-Remission Therapy

A

Only for those who received intensive chemo

High dose Cytarabine (HiDAC)
- gold standard
- can add midostaurin for FLT3+
- if GO was given during induction it can be added here as well (days 1&2 only)

Liposomal daunorubicin + cytarabine
- if given during induction

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12
Q

Low intensity chemo options

A

Azacytidine + Venetoclax
Low dose Cytarabine (LDAC) + Venetoclax
Ivosidenib + Venetoclax
- only in IDH1
LDAC + Glasdegib

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13
Q

Venetoclax DDI dose adjustments (Azacitidine backbone)

A

posaconazole / voriconazole: 100mg Venetoclax QD

isavuconazole, diltiazem, verapamil, amiodarone, carvedilol: 200 mg Venetoclax QD

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14
Q

Venetoclax DDI dose adjustments (LDAC backbone)

A

posaconazole / voriconazole: 150 mg Venetoclax QD

Isavuconazole, diltiazem, verapamil, amiodarone, carvedilol: 300 mg Venetoclax QD

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15
Q

AML targeted therapy pearls

A

Midostaurin
- FDA approved for new FLT3+ AML
- not FDA approved for relapsed/refractory

Gilteritinib
- FDA approved for relapsed/refractory FLT3+ AML

Ivosidenib
- FDA approved for new and relapsed/refractory IDH1+ AML

Enasidenib
- FDA approved for relapsed/refractory IDH2+ AML

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16
Q

Supportive Care AML:
Transfusions

A

RBC transfusion if Hgb < 8

Platelet transfusion if platelets < 10,000

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17
Q

Supportive Care AML
Infection prophylaxis (HSV/VZV)

A

Acyclovir

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18
Q

Supportive Care AML
Infection prophylaxis (antibacterial)

A

Levofloxacin
- or ciprofloxacin

if allergic to fluoroquinolones:
Augmentin or 3rd gen Cephalosporin

19
Q

Supportive Care AML
Infection prophylaxis (Fungal & Mold)

A

Posaconazole***

voriconazole (does not cover mold)

20
Q

Tumor Lysis Syndrome

A

Oncologic emergency: rapid tumor breakdown following chemo -> release of potassium, phosphorus, and uric acid

presentation:
- hyperuricemia
- hyperphosphatemia
- hyperkalemia
- N/V/D
- edema
- acute renal failure
- hematuria, uremia
- CHF, dysrhythmias
- syncope
- seizure
- death

21
Q

TLS prophylaxis

A

Allopurinol
- prevents conversion of hypoxanthine and xanthine to uric acid

hydration

Rasburicase
- only for high risk + pre-existing hyperuricemia

22
Q

TLS Management:
Hyperuricemia

A

IV hydration
Rasburicase

23
Q

TLS Management:
Hyperkalemia

A

EKG -> rule out active arrhythmia
sodium polystyrene sulfonate
insulin & glucose
dialysis

24
Q

TLS Management:
Hyperphosphatemia

A

phosphate binders
- sevelamer
- calcium acetate

dialysis

25
Q

TLS Management:
Hypocalcemia

A

DO NOT TREAT

26
Q

Anthracycline (daunorubicin, idarubicin, mitoxantrone) Clinical Pearls

A

ADE:
- red urine / sclera
- Mitoxantrone: blue-green urine
- myelosuppression
- cardiac toxicity

27
Q

Cytarabine Clinical Pearls

A

ADE:
- neurotoxicity -> “neuro checks” required prior to each dose
- conjunctivitis

28
Q

GO Clinical Pearls

A

ADE:
- infusion rxns -> pre-medicate with APAP, diphenhydramine, and methylprednisolone
- BBW hepatotoxicity

29
Q

Low intensity chemo Clinical Pearls

A

ADE:
- constipation -> standing bowel meds
- low to moderate emetogenicity -> pre-med with ondansetron

30
Q

G-CSF

A

Filgrastim
Sargramostim
Use: severe infections in setting of neutropenia
May be started after day 14 bmbx in pts receiving intensive chemo
ADE:
- bone pain -> manage with loratadine or hydroxyzine
- fever
- injection site rxn
- risk of potentiating leukemic cells

31
Q

Chronic Myeloid Leukemia Treatment

A

Tyrosine Kinase Inhibitors
- goal: complete cytogenic response within 12 months
- if complete hematologic response not achieved within 3 months -> change therapy

32
Q

Tyrosine Kinase Inhibitors

A

1st gen: Imatinib
2nd gen: Dasatinib, Nilotinib
3rd gen: Bosutinib, Ponatinib
STAMP inhibitor (targets ABL1 Myristoyl Pocket): Asciminib

33
Q

Imatinib (Gleevec)

A

First gen TKI
MOA: selective inhibitor of BCR-ABL tyrosine kinase
Dosing: 400mg PO QD
- doses > 400 are not recommended in new patients -> more side effects, dose interruptions and higher rates of non-compliance

Some resistance has been developed to this drug -> try newer TKI

ADE:
- Edema/fluid retention
- myalgias
- hypophosphatemia
- GI (diarrhea, N/V)

34
Q

Dasatinib (Sprycel)

A

2nd Gen TKI
MOA: dual inhibitor of BCR-ABL and Src family of kinases
MUCH more potent than imatinib
ADE:
- Pleural/pericardial effusions
- bleed risk
- pulmonary arterial hypertension

35
Q

Nilotinib (Tasigna)

A

2nd gen TKI
more potent than imatinib
BBW: QTc prolongation
ADE:
- elevated pancreatic enzymes
- indirect hyperbilirubinemia
- QTc prolongation
- Cardiovascular events

36
Q

Bosutinib (Bosulif)

A

3rd gen TKI
MOA: dual activity against BCR-ABL, Src, Lyn, and Hck kinases
- activity against many BCR-ABL mutations that are resistant to imatinib, dasatinib, and nilotinib
ADE:
- GI (Diarrhea, N/V)
- headache
- rash

37
Q

CML Preferred initial treatments in low risk patients

A

First gen: Imatinib
OR
Second gen:
- Dasatinib
- Nilotinib

38
Q

Contraindicated mutations in TKI treatment

A

Bosutinib: T3151, V299L, G25E, F317L
Dasatinib: T3151/A, F317L/V/I/C, V299L
Nilotinib: T3151, Y253H, E255K/V, F359V/C/I, G250E
Asciminib, Ponatinib, Omacetaxine, allo HCT, clinical trial: None

39
Q

Ponatinib (Iclusig)

A

Third gen TKI
Active against all BCR-ABL point mutation INCLUDING: T315I
BBW: vascular occlusion, heart failure, hepatotoxicity
ADE:
- elevated pancreatic enzymes
- hypertension
- skin toxicity
- thrombotic events

40
Q

Asciminib (Scemblix)

A

STAMP inhibitor
targets the ABL1 Myristoyl Pocket
Allosteric inhibitor
Indication: for pts who have previously received 2+ TKIs or those with T315I mutation

41
Q

Omacetaxine mepesuccinate (Synribo)

A

FDA approved for patients with resistance and/or intolerance or two or more TKIs
MOA: reversible inhibitor of protein synthesis
ADE:
- myelosuppression
- nausea
- diarrhea
- fever

42
Q

CML Accelerated Phase Treatment

A

TKIs
- 2nd gen preferred (dasatinib, nilotinib, bosutinib)
- selection based on prior therapy and cytogenetics

Omacetaxine can be considered in cases of disease progression due to resistance or intolerance to 2+ TKIs

Allogenic transplant may be considered

43
Q

CML Blast Crisis Treatment

A

TKI +/- chemotherapy followed by allogenic HSCT
chemo chosen based on subtype of disease

Therapeutics P3 Spring (32 decks)

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