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Oncology Therapeutics > Acute Myeloid Leukemia (AML) > Flashcards

Acute Myeloid Leukemia (AML) Flashcards

1
Q

Classification of Leukemia :

1) Myeloid = defect in the cells of the ?
2) Lymphoid = defect in the cells of the ?
3) Acute means?
4) Chronic means?

A
  1. Defect in cells of myeloid line (granulocytes, monocytes, erthyrocytes)
  2. Defect in cells of lymphoid line ( b cells and t cells)
  3. Aggressive, rapid course (weeks), immature cells
  4. prolonged course (years) , more mature cells
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2
Q

Acute Myeloid Leukemia : RIsk Factors
-Largely unknown!

  1. Enviro exposure such as?
  2. Genetics such as?
  3. Exposure to ____
A
  1. radiation , chemical exposure, cig smoke, immunologic disposition
  2. Down syndrome and fanconi anemia
  3. Alkylating agents/topoisomerase II inhibs
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3
Q

AML Clinical Features and SIgns/Sx’s

  1. BM failure such as ? (3)
  2. Abrupt onset of sx’s such as ?
  3. L____ where WBC may be high, low or normal
  4. Derm Sx’s such as ?
  5. Lab abnorms such as ? (3)
  6. P__
A
  1. Anemia, Thrombocytopenia, Neutropenia
  2. Infection, SOB, extreme fatigue/malaise, pallor, easy bruising, weight loss/anorexia
  3. Leukocytosis
  4. Gingival Hyperplasia/leukemic cutis (seen w/monocytic variants)
  5. Renal insufficiency, incr LDH, Incr URIC ACID
  6. Pain
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4
Q

Key points of TX :
1) Whats the goal of therapy ?
2) Maintaining what is critical for all pt’s?
3) What’s the goal of induction therapy ?
4) Primary tx modality?
5) Most important predictors of outcomes in AML? (4)
6) Should initiate tx when ?
7) modify tx based on ?

A
  1. Cure is long term goal of therapy for many patients
  2. QOL , especially for older pt’s who may not be transplant candidates
  3. Achieve complete remission
  4. Chemotx
  5. Age (if >= 60 associated with a decr in overall survival)
    -Performance status (ECOG)
    -Cytogenetics
    -Duration of first complete remission (CR)
    CR < 6 months is poor while CR > 12 months is more favorable
  6. Immediately after definitive diagnosis made
  7. pt comordbidities
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5
Q

Tx Course - NO targetable Mutations

  1. Induction ? If donor is immed available
  2. Consolidation ?
  3. Maintenance?
  4. Induction if donor is NOT immed available
  5. Consolidation ?
  6. Maintenance?
A
  1. 7+3 –> CR (Donor immed available)
  2. Allogeneic HCT
  3. CLinical trial if available
  4. 7+3 –> CR
  5. HiDAC x 1-2 cycles –> Allogeneic HCT
  6. CLinical trial if available
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6
Q

TX course if FLT3 +

  1. Induction ? (Donor not immed available)
  2. Consolidation ?
  3. Maintenance
A
  1. 7+3 + Midostaurin/quizartinib –> CR
  2. HiDAC + Midostaurin/quizartinib x 1-2 cycles –> Allogeneic HCT
  3. Sorafenib, Midostaurin, Quizartinib gilteritinib or clinical trial, if available for a min of 2 yrs (depending on tolerance)
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7
Q

So what exactly is 7+3?

A

Cytarabine 100-200mg/m2 IVCI x 7 days + Idarubicin 12 mg/m2 IV daily x 3 days or Daunorubicin 60- 90mg/m2 IV daily x 3 days.

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8
Q
  1. What is Ara-C?
  2. Standard dose Ara-C ?
  3. High Dose Ara-C (hiDAC) ?
A
  1. Cytarabine
  2. 100-200 mg/m2 IVCI over 7 days used during “7” portion of induction
  3. 1.5- 3g/m2 IV q12h over 3 hours x 6 total doses on days 1,2, 3 or 1,3,5

Consolidation in a patient < 60 who does not have a donor available immediately

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9
Q

FDA approved agents for AML :

  1. Midostaurin
    -Don’t need to ___ w/ ____
    -Smells ___
    N
    Q
    __ substrate
    -Only for ???
  2. Gilteritinib
    - Ae’s ?
  3. Quizartinib
    - Used in combo with standard ___ and ____, and as ___ following ____
    -ONLY FOR ____
    -BBW in patients with ? (4)
    -What must you perform in patients prior to initiation and then once weekly during induction and consolidation , and then weekly for a month during maintenance?
A
  1. Dose adjust, strong 3A4 inhibs

terrible
nausea
qtc prolongation
3A4 substrate
Newly diagnosed FLT3 ITD or TKD mutated AML

  1. QTC prolongation and its a 3A4 substrate
  2. Quizartinib
    - 7+3 induction , HiDAC, maintenance monotherapy, consolidation chemotherapy
  • newly diagnosed FLT3-ITD mutated AML

-Severe hypokalemia, severe hypomag, long QT syndrome, or in pt’s with hx of ventricular arrhythmias or TdP

  • ECGS
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10
Q
  1. Ivosidenib : What is it approved for?
    -AE’s?
  2. Enasidenib : Only approved for?
    -AE’s?
  3. Olutasidenib : FDA approval granted for ?
    -AE”s?
A
  1. Newly diagnosed and relapsed or refractory AML w/susceptible IDH1 mutation
  • QT interval prolongation, IDH-DS, anemia, thrombocytopenia, leukocytosis
  1. relapsed or refractory IDH2 Mutated AML
    -Hyperbilirubinemia, IDH differentiation syndrome, Anemia, thrombocytopenia
  2. R/R AML. No OS data avail yet
    - Differntiation syndrome
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11
Q
  1. Liposomal Daunorubicin + Cytarabine
    -CAn be used for both __ and ___?
    -CANNOT BE SUBBED for ?
    -Approved only for pts with ????
    -Can cause prolonged ___
  2. Venetoclax + Azacitidine/decitabine
    -Only approved for ?
    -Significant ____
    -____ with ramp up dosing
  3. Gemtuzumab Ozogamicin
    -Req premed with ?
    -Close monitoring for ?
    -Approved in which disease ?
A
  1. induction , maintenance

standard 7+3
- THERAPY RELATED AML (AKA secondary AML) or AML with myelodysplasia related changes (AML-MRC)

Myelosuppression and therefore increased LOS

  1. Newly diagnosed AML >= 75 yo or who have comorbidities that preclude use of intensive induction chemotx
    - Myelosuppression
    -Pill burden
  2. Tylenol, benadryl, and methylpred 1mg/kg
  • hepatotoxicity/veno occlusive disease, thrombocytopenia/hemorrhage, transient infusion reactions
  • CD33 Positive disease only
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12
Q

How is Complete remission (CR) defined?
1. Absolute neutrophil count of ?
2. Platelet count of ?
3. Pt independent of ?
4. Bone marrow with < ___
5. Absence of _____

A
  1. > 1000mCL
  2. > = 1000,000 mCL
  3. Transfusions
  4. <5% blasts
  5. Blasts with Auer Rods
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13
Q

Suppportive Care : infxn prophylaxis

  1. Bacterial prophylaxis recc when neutropenia is expected to be ?

2.Fungal prophylaxis warranted due to ?
-High risk for what kinda infections?
-In prophylactic setting which agent improves overall survival?

  1. Viral Prophylaxis
    -Warranted due to ?
    -we assume everyone is ?
  2. White blood cell stimulating factors
    -Is it recc during induction ?
    -Maybe considered during consolidation in setting of ? (2)
    -Shouldnt be used within how many days of a BM biopsy due to potential to confound results
A
  1. > 7 days
  2. Prolonged neutropenia
    - mold and yeast
    - posaconazole
  3. prolonged neutropenia in all pt’s
    -HSV+
  4. NOT recc during induction
    -Life threatening infections or sepsis
    - 7 days
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14
Q

Cytarabine induced Ocular Toxicity

  1. Which doses ?
  2. Sx’s?
  3. Onset ?
  4. WHat can you use to prevent it?
A
  1. Cytarabine doses >=1 gm/m^2 IV over 1-4hrs for > 2 doses
  2. excessive tearing , pain, photophobia
  3. 2-4 days after 1st dose and continues for 2-3 days after last dose
  4. Steroid eye drops QID during HiDAC and for 48h after completion of HiDAC –> Prednisolone 2% eye drops 2 drops OU TID
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15
Q

Cytarabine Induced Cerebellar toxicity
1. Risk factors ?
2. Monitoring for ?
3. Onset of?
4. WHat to do if Scr rising secondary to TLS?
5. WHat to do if devel of cerebellar toxicity ?

A
  1. Renal insufficiency
    > 60
    patients receiving HiDAC
  2. Neuro exam prior to each dose of HiDAC such as nystagmus, slurred speech , ataxia/dysmetria
  3. 3-8 days after tx or after several doses
  4. hold HiDAC until renal insuff resolves
  5. DC HiDAC and do not rechallenge
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16
Q

IDH-Inhibitor Differentiation Syndrome
1. Onset ?
2. Sx’s ?

A
  1. 7-10 days to 5 months after initiation
  2. Fever
    * Rapid weight gain/edema
    * Respiratory symptoms
    * Pleural/peri-cardiac effusions
    * Hypotension
    * Acute renal failure
17
Q

See chart for Prophylaxis regimens and duration

A

See chart

Oncology Therapeutics (17 decks)

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