Jorge E. Cortes, MD, and Stephen A. Strickland, MD, MSCI, prepared useful practice aids pertaining to acute myeloid leukemia for this CME activity titled "Novel Induction Options in AML: Assessing the Implications for HCT-Eligible Patients." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2u4yk5p. CME credit will be available until April 3, 2019.

1. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Management of HCT-Eligible AML Patients:
Induction, Post-Induction, and Post-Remission Therapy
PRACTICE AID
Access the activity,“Novel Induction Options in AML: Assessing the Implications for HCT-Eligible Patients,”at
www.peerview.com/XQY.
≥60 Years of Age1
<60 Years of Age1
Induction
• Standard-dose cytarabine + idarubicin or daunorubicin
• Standard-dose cytarabine + daunorubicin and cladribine
• High-dose cytarabine + idarubicin or daunorubicin
• Standard-dose cytarabine + daunorubicin and midostaurin (FLT3-mutated AML)
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for therapy-related AML
other than CBF/APL, or patients with antecedent MDS/CMML, or cytogenetic changes
consistent with MDS
• Standard-dose cytarabine + daunorubicin and gemtuzumab ozogamicin (CD33-positive)
• Fludarabine, high-dose cytarabine after fludarabine, idarubicin, and G-CSF
• Lower intensity therapy
(HMAs) or low-dose cytarabine
• Gemtuzumab ozogamicin
(CD33-positive)
• Enasidenib (IDH2-mutated AML)
• BSC
• Additional standard-dose cytarabine + anthracycline or mitoxantrone
• Standard-dose cytarabine + daunorubicin and midostaurin
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for
therapy-related AML other than CBF/APL, or patients with antecedent MDS/CMML,
or cytogenetic changes consistent with MDS
• Intermediate-dose cytarabine-containing regimens
• Reduced-intensity allogeneic HCT
• Await recovery
• BSC
If significant cytoreduction with low % residual blasts
• Standard-dose cytarabine + idarubicin or daunorubicin
• Standard-dose cytarabine + daunorubicin and midostaurin
Post-Induction
Yes No
Unfavorable
Prognostic
Features?
Yes
No
(De novo AML)
Residual Disease
in Candidates
for Intensive
Therapy?
Hypoplasia Await recovery
After
Standard-Dose
Cytarabine
After
High-Dose
Cytarabine
If significant residual disease
without a hypocellular marrow
• Matched sibling or alternative
donor HCT
• BSC
• Standard-dose cytarabine + idarubicin or daunorubicin or mitoxantrone
• Standard-dose cytarabine + daunorubicin and midostaurin (FLT3-mutated AML)
• Standard-dose cytarabine + daunorubicin and gemtuzumab ozogamicin (CD33-positive)
• Lower-intensity therapy (HMAs)
• Standard-dose cytarabine + idarubicin or daunorubicin or mitoxantrone
• Standard-dose cytarabine + daunorubicin and midostaurin (FLT3-mutated AML)
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for
therapy-related AML other than CBF/APL, or patients with antecedent MDS/CMML,
or cytogenetic changes consistent with MDS
No
Yes
Clinical note: liposomal daunorubicin-cytarabine (CPX-351) is now approved for the treatment of adults with newly diagnosed therapy-related AML or AML with myelodysplasia-related
changes (AML-MRC); phase 3 evidence also showed that use of CPX-351 as induction led to improved survival post-transplant vs 7+3.2,3
If significant residual disease without a hypocellular marrow
• Cytarabine
• Standard-dose cytarabine + idarubicin or daunorubicin
• Standard-dose cytarabine + daunorubicin and midostaurin
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for
therapy-related AML other than CBF/APL, or patients with antecedent
MDS/CMML, or cytogenetic changes consistent with MDS
Candidate
for Intensive
Therapy?

2. Management of HCT-Eligible AML Patients:
Induction, Post-Induction, and Post-Remission Therapy
AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; BSC: best supportive care; CBF: core-binding factor; CD: cluster of differentiation; CMML: chronic myelomonocytic leukemia; FLT3: fms-like tyrosine kinase 3; G-CSF: granulocyte colony-stimulating factor;
HCT: hematopoietic stem cell transplantation; HMAs: hypomethylating agents; IDH2: isocitrate dehydrogenase 2; MDS: myelodysplastic syndrome; PS: performance status.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 1.2018. 2. Lancet JE et al. 2017 Annual BMT Tandem Meetings (BMT Tandem 2017). Abstract 19. 3. Vyxeos (daunorubicin and cytarabine)
Prescribing Information. https://www.accessdata.fda. gov/drugsatfda_docs/label/2017/209401s000lbl.pdf. Accessed February 6, 2018.
PRACTICE AID
Access the activity,“Novel Induction Options in AML: Assessing the Implications for HCT-Eligible Patients,”at
www.peerview.com/XQY.
≥60 Years of Age1
<60 Years of Age1
• Matched sibling/alternative donor HCT
• High-dose cytarabine
• High-dose cytarabine and midostaurin (FLT3-mutated AML)
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for
therapy-related AML other than CBF/APL, or patients with antecedent
MDS/CMML, or cytogenetic changes consistent with MDS
• BSC
Post-Remission(Consolidation)Therapy
Previous
Intensive
Therapy
Yes
Yes
No
No
Response?
Previous
Low-Intensity
Therapy
Poor-Risk
Cytogenetics/
Molecular
Abnormalities
• Reduced-intensity HCT
• Clinical trial
• Standard-dose cytarabine ± anthracycline (idarubicin or daunorubicin)
• Consider intermediate-dose cytarabine in patients with good PS, normal renal
function, and better-risk/normal karyotype with favorable molecular markers
• Intermediate-dose cytarabine with midostaurin
• Liposomal encapsulation of cytarabine and daunorubicin (CPX-351) for therapy-related
AML other than CBF/APL, or patients with antecedent MDS/CMML,
or cytogenetic changes consistent with MDS
• Standard-dose cytarabine + daunorubicin and gemtuzumab ozogamicin (CD33-positive)
• Maintenance with HMAs until progression (if patient received HMAs during induction)
• Observation
Induction failure
• Allogeneic HCT (preferably in clinical trial)
• BSC
CBF
Translocations
Treatment-
Related
DiseaseOr
Complete
Response?
• High-dose cytarabine
• Standard-dose cytarabine + daunorubicin and gemtuzumab ozogamicin
(CD33-positive)
No KIT Mutation
or Favorable-Risk
Molecular
Abnormalities
• Matched sibling or alternative donor HCT
• High-dose cytarabine
• High-dose cytarabine and midostaurin (FLT3-mutated AML)
• Standard-dose cytarabine + daunorubicin and gemtuzumab ozogamicin
(CD33-positive)
Intermediate-Risk
Cytogenetics/
Molecular
Abnormalities
• Reduced-intensity HCT
• Continue HMA therapy every 4-6 weeks until progression
• Gemtuzumab ozogamicin (CD33-positive)
• Continue enasidenib until progression (IDH2-mutated AML)

3. This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
A Snapshot of Innovative Therapies in AML:
Current Status, Dosing, and Other Considerations
a
For additional induction use d 1 and 3 for subsequent cycles, if needed; for consolidation: daunorubicin 29 mg/m2
and cytarabine 65 mg/m2
liposome IV over 90 mins on d 1 and 3.
AE: adverse event; AML: acute myeloid leukemia; AML-MRC: AML with myelodysplasia-related changes; CD: cluster of differentiation; CT: chemotherapy; FLT3: fms-like tyrosine kinase 3; FN: febrile neutropenia; IDH1: isocitrate dehydrogenase 1; IDH2: isocitrate dehydrogenase 2;
R/R: relapsed or refractory; t-AML: therapy-related acute myeloid leukemia.
1. Lancet JE et al. 2016 Annual Meeting of the American Society of Clinical Oncology (ASCO 2016). Abstract 7000. 2. Lancet JE et al. 2017 Annual BMT Tandem Meetings (BMT Tandem 2017). Abstract 19. 3. Vyxeos (daunorubicin and cytarabine) Prescribing Information. https://www.accessdata.fda.
gov/drugsatfda_docs/label/2017/209401s000lbl.pdf. Accessed February 6, 2018. 4. Rydapt (midostaurin) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/207997s000lbl.pdf. Accessed February 6, 2018. 5. Idhifa (enasidenib) Prescribing Information. https://
www.accessdata.fda.gov/drugsatfda_docs/label/2017/209606s000lbl.pdf. Accessed February 6, 2018. 6. https://clinicaltrials.gov/ct2/show/NCT03173248. Accessed February 6, 2018. 7. Mylotarg (gemtuzumab ozogamicin) Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/
label/2017/761060lbl.pdf. Accessed February 6, 2018.
PRACTICE AID
Access the activity,“Novel Induction Options in AML: Assessing the Implications for HCT-Eligible Patients,”at
www.peerview.com/XQY.
DRUG
Midostaurin4
STATUS
TARGET/
FORMULATION
DOSE CONSIDERATIONS
Approved
Plus CT in FLT3-mutant AML FLT3
50 mg orally twice
daily with food
q GI events most common
q Promote therapy adherence
q Be mindful of potential
drug–drug interactions
Enasidenib5
Approved
R/R IDH2-mutation–positive AML
IDH2 100 mg orally daily
Monitor for:
q IDH-differentiation syndrome
q GI events
q Elevated bilirubin
Ivosidenib6
Phase 3; under FDA review
R/R IDH1-mutation–positive AML
IDH1 500 mg orally daily
Most common AEs in trials:
q Diarrhea, leukocytosis, nausea,
fatigue, and FN
q IDH-differentiation syndrome also reported
CPX-3511-3
Approved
Adults with newly diagnosed
t-AML or AML-MRC
Liposomal
cytarabine
+ daunorubicin
5:1 molar ratio
Induction: daunorubicin 44 mg/m2
and
cytarabine 100 mg/m2
liposome IV
over 90 mins d 1, 3, and 5a
q Monitor blood counts regularly
until recovery
q Not recommended in pts with
cardiac function less than normal
Gemtuzumab
ozogamicin7
Approved
Newly diagnosed CD33-positive AML
in adults, R/R CD33-positive AML
in adults, and in pediatric pts aged ≥2 y
CD33
Induction: 3 mg/m2
(up to one
4.5 mg vial) d 1, 4, and 7 in
combination with daunorubicin
and cytarabine
q Infusion-related reactions
q Premedicate with corticosteroid,
antihistamine, and acetaminophen
q Monitor platelet counts