Alexander Perl, MD, and James M. Foran, MD, FRCPC, prepared useful practice aids pertaining to leukemia for this CME activity titled "Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2EZE2I6. CME credit will be available until March 28, 2020.

1. A Snapshot of Innovative Therapies in AML
Current Status, Dosing, and Other Considerations
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
Access the activity,“Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance,”at
PeerView.com/PCE40.
STATUS DOSEDRUG CONSIDERATIONSTARGET
Approved
Plus chemotherapy in adults with newly
diagnosed FLT3-mutation–positive AML
50 mg orally twice daily with food on
d 8-21 of each induction cycle with
cytarabine and daunorubicin and on
d 8-21 of each consolidation cycle with
high-dose cytarabine
Midostaurin4
q GI events most common
q Promote therapy adherence
q Be mindful of potential drug–drug interactions
FLT3
Approved
Adults with R/R
IDH2-mutation–positive AML
100 mg orally daily
Enasidenib10
Monitor for:
q IDH-differentiation syndrome
q GI events
IDH2 q Elevated bilirubin
q Leukocytosis
Approved
Adults with R/R
IDH1-mutation–positive AML
500 mg orally daily
Ivosidenib11
Monitor for:
q IDH-differentiation syndrome
q Guillain-Barré syndrome
IDH1 q QT prolongation
q GI events, nausea,
leukocytosis
Breakthrough Therapy Designation
August 2018 (Under Priority Review)
Adults with newly diagnosed and R/R
FLT3-ITD–positive AML
60 mg used in phase 3 QuANTUM-R
study (30-mg lead-in)Quizartinib6-9
q Most common AEs in early studies included nausea,
prolonged QT interval, vomiting, and dysgeusia
FLT3
Approved
Adults with newly diagnosed
t-AML or AML-MRC
Induction: daunorubicin 44 mg/m2
and
cytarabine 100 mg/m2
liposome IV
over 90 min on d 1, 3, and 5a
CPX-3511-3
q Can cause prolongation of blood count suppression;
monitor blood counts regularly until recovery
q Not recommended in patients with decreased cardiac
function
Cytotoxic therapy
(liposomal cytarabine
+ daunorubicin
5:1 molar ratio)
Approved
Adults with FLT3-mutation–positive
R/R AML
120 mg orally daily
Gilteritinib5
q Most common AEs include myalgia/arthralgia,
transaminase increase, fatigue/malaise, noninfectious
diarrhea, dyspnea, edema, rash, pneumonia, nausea,
stomatitis, cough, headache, hypotension, dizziness,
and vomiting
FLT3
Approved
In combination with azacitidine or
decitabine or low-dose cytarabine for
newly diagnosed AML in adults
≥75 years or who have comorbidities
that preclude use of intensive
induction chemotherapy
BCL-2
Ramp-up phase: 100 mg orally on d 1,
200 mg on d 2, 400 mg on d 3;
d 4 and beyond: 400 mg (with HMA)
or 600 mg (with low-dose cytarabine)
q Most common AEs as part of combination therapy in
AML include nausea, diarrhea, thrombocytopenia,
constipation, neutropenia, febrile neutropenia, and
fatigue (among others)b
q Standard monitoring and prophylaxis measures for TLS
are recommended
Venetoclax12

2. 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 min on d 1 and 3. b
See prescribing information for a complete list of common AEs with venetoclax combinations in AML.12
AE: adverse event; AML: acute myeloid leukemia; AML-MRC: AML with myelodysplasia-related changes; BM: bone marrow; CD: cluster of differentiation; FLT3: fms-like tyrosine kinase 3; FN: febrile neutropenia; HCT: hematopoietic cell transplantation; Hhp: hedgehog pathway; HMA: hypomethylating
agent; IDH: isocitrate dehydrogenase; ITD: internal tandem duplication; mAb: monoclonal antibody; R/R: relapsed or refractory; t-AML: therapy-related acute myeloid leukemia; TLS: tumor lysis syndrome; VOD: veno-occlusive disease.
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. http://pp.jazzpharma.com/pi/vyxeos.
en.USPI.pdf. Accessed January 8, 2019. 4. Rydapt (midostaurin) Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/rydapt.pdf. Accessed January 8, 2019. 5. Xospata (gilteritinib) Prescribing Information. https://astellas.us/docs/xospata.pdf. Accessed
January 8, 2019. 6. https://clinicaltrials.gov/ct2/show/NCT02668653. Accessed January 8, 2019. 7. https://clinicaltrials.gov/ct2/show/NCT02039726. Accessed January 8, 2019. 8. Cortez J et al. 23rd Congress of the European Hematology Association (EHA 2018). Abstract LB2600. 9. https://pharmaphorum.
com/market-access-2/fda-grants-leukaemia-drug-breakthrough-status/. Accessed January 8, 2019. 10. Idhifa (enasidenib) Prescribing Information. https://media.celgene.com/content/uploads/idhifa-pi.pdf. Accessed January 8, 2019. 11. Tibsovo (ivosidenib) Prescribing Information. https://www.tibsovo.
com/pdf/prescribinginformation.pdf. Accessed January 8, 2019. 12. Venclexta (venetoclax) Prescribing Information. https://www.rxabbvie.com/pdf/venclexta.pdf. Accessed January 8, 2019. 13. Mylotarg (gemtuzumab ozogamicin) Prescribing Information. http://labeling.pfizer.com/ShowLabeling.
aspx?id=9548. Accessed January 8, 2019. 14. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm626443.htm. Accessed January 8, 2019. 15. Daurismo (glasdegib) Prescribing Information. http://labeling.pfizer.com/ShowLabeling.aspx?id=11336. Accessed January 8, 2019.
16. Agura E et al. 60th American Society of Hematology Annual Meeting and Exposition (ASH 2018). Abstract 1017. 17. Roboz GJ et al. FutureOncol. 2016;12:293-302.
Access the activity,“Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance,”at
PeerView.com/PCE40.
A Snapshot of Innovative Therapies in AML
Current Status, Dosing, and Other Considerations
PRACTICE AID
DRUG STATUS TARGET DOSE CONSIDERATIONS
Glasdegib14,15
Approved
In combination with low-dose cytarabine
for newly diagnosed AML in adults
≥75 years or who have comorbidities
that preclude use of intensive
induction chemotherapy
Hhp 100 mg orally daily
q Most common AEs include anemia, fatigue,
hemorrhage, FN, musculoskeletal pain, nausea,
edema, thrombocytopenia, and dyspnea
q See label for other common AEs and for information
on the potential for embryo-fetal toxicity and appropriate
management approaches
Gemtuzumab
ozogamicin13
Approved
Newly diagnosed CD33+ AML in adults,
R/R CD33+ AML in adults, and in
pediatric patients aged ≥2 years
CD33
Induction: 3 mg/m2
(up to one
4.5-mg vial) on 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 frequently (hemorrhage) and
signs/symptoms of liver toxicity (VOD)
Phase 3 SIERRA study
Adults aged ≥55 years with active,
R/R AML, adequate organ function,
and related/unrelated matched donor
CD45
(BC8 mAb
linked to
radioisotope
iodine-131)
Dosimetry directed
(SIERRA study)
Iomab-B16
Phase 2 data
Maintenance therapy post-HCT in AML
Ongoing phase 3 QUAZAR study
Maintenance therapy in adults aged
≥55 years with AML in first complete
remission; HCT-ineligible AML
Epigenetic
modification
(novel oral
formulation
of HMA)
300 mg orally daily for 14 d of 28-d
treatment cycles (QUAZAR study)Oral
azacitidine17
q In phase 3 SIERRA trial, conditioning with Iomab-B
appeared feasible in patients with active disease and
high BM blast burden
q AEs included FN, stomatitis, malnutrition, epistaxis,
sepsis, hypotension, hypobilirubinemia, fatigue
q In early studies in the post-HCT maintenance setting,
grade 3/4 AEs included vomiting, thrombocytopenia,
diarrhea, and nausea

3. Access the activity,“Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance,”at
PeerView.com/PCE40.
Management of HCT-Eligible AML Patients
Induction, Post-Induction, and Post-Remission Therapy
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
≥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 preferred, low-dose
cytarabine)
• Gemtuzumab ozogamicin (CD33-positive)
• Enasidenib (IDH2-mutated AML) or ivosidenib
(IDH1-mutated AML)
• Venetoclax + decitabine
• Venetoclax + azacitidine
• Venetoclax + low-dose cytarabine
• Glasdegib + low-dose cytarabine
• 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)
Hypoplasia
Residual
Disease
After Standard-Dose
Cytarabine in
Candidates for
Intensive Therapy
Await recovery
After
Standard-Dose
Cytarabine
After
High-Dose
Cytarabine
If significant residual disease
without a hypocellular marrow
• Matched sibling or
alternative donor HCT
• Therapy for R/R disease
• 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)
• Venetoclax + decitabine
• Venetoclax + azacitidine
• 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 that are
consistent with MDS
Clinical note: Novel therapeutics currently being assessed in the HCT setting in AML include the radioimmunoconjugate Iomab-B (as pretransplant conditioning)2
and oral azacitidine as an HMA maintenance option.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?

4. 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
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 3.2018. 2. Agura E et al. 60th American Society of Hematology Annual Meeting and Exposition (ASH 2018). Abstract 1017. 3. Roboz GJ et al. Future Oncol. 2016;12:293-302.
Access the activity,“Integrating Innovative Therapeutics With Allogeneic HCT in AML: Insights and Evidence From Induction to Maintenance,”at
PeerView.com/PCE40.
Management of HCT-Eligible AML Patients
Induction, Post-Induction, and Post-Remission Therapy
PRACTICE AID
≥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
• Standard-dose cytarabine ± anthracycline (idarubicin or daunorubicin)
• Consider intermediate-dose cytarabine in patients with good PS, normal renal function,
and better-risk or normal karyotype with favorable molecular markers
• Intermediate-dose cytarabine with midostaurin
• Liposomal encapsulation 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
• Cytarabine 1,000 mg/m2
+ daunorubicin + 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
• Cytarabine 1,000 mg/m2
+ 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)
• Cytarabine 1,000 mg/m2
+ daunorubicin and gemtuzumab
ozogamicin (CD33-positive)
Intermediate-Risk
Cytogenetics/
Molecular
Abnormalities
• Reduced-intensity HCT
• Continued HMA therapy every 4-6 wk until progression
• Gemtuzumab ozogamicin (CD33-positive)
• Continue enasidenib or ivosidenib until progression (IDH2-mutated AML)
• Continue venetoclax + decitabine
• Continue venetoclax + low-dose cytarabine
• Continue glasdegib + low-dose cytarabine