Harry P. Erba, MD, PhD, and James M. Foran, MD, FRCPC, prepared useful Practice Aids pertaining to acute myeloid leukemia for this CME activity titled "The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2vdoO1j. CME credit will be available until March 12, 2021.

1. Access the activity,“The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant,”
at PeerView.com/WRR40
A Snapshot of Innovative Therapies in AML
Current Status, Dosing, and Other Considerations
PRACTICE AID
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
Phase 3 testing
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
AML: acute myeloid leukemia; AML-MRC: AML with myelodysplasia-related changes; BCL-2: B cell lymphoma 2; 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; MDS: myelodysplastic syndrome; RFS: relapse-free survival; 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. 52nd 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 29, 2020. 4. Rydapt (midostaurin) Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/rydapt.pdf. Accessed January 29, 2020. 5. Xospata (gilteritinib) Prescribing Information. https://astellas.us/docs/xospata.pdf. Accessed
January 29, 2020. 6. https://clinicaltrials.gov/ct2/show/NCT02668653. Accessed January 29, 2020. 7. https://clinicaltrials.gov/ct2/show/NCT02039726. Accessed January 29, 2020. 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 29, 2020. 10. Idhifa (enasidenib) Prescribing Information. https://media.celgene.com/content/uploads/idhifa-pi.pdf. Accessed January 29, 2020. 11. Tibsovo (ivosidenib) Prescribing Information. https://www.tibsovo.
com/pdf/prescribinginformation.pdf. Accessed January 29, 2020. 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 29, 2020. 14. https://www.fda.gov/drugs/fda-approves-glasdegib-aml-adults-age-75-or-older-or-who-have-comorbidities. Accessed January 29, 2020. 15. Daurismo (glasdegib) Prescribing Information. http://labeling.pfizer.com/ShowLabeling.aspx?id=11336. Accessed
January 29, 2020. 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. 18. Wei AH et al. 61st Annual Meeting and Exposition of the American Society of Hematology (ASH 2019). Abstract LBA-3.
Access the activity,“The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant,”
at PeerView.com/WRR40
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 as maintenance therapy
post-HCT in AML
Phase 3 QUAZAR study
Maintenance with oral azacitidine in
adults aged ≥55 years with AML in
first complete remission induced
substantial improvements in OS and
RFS following induction chemotherapy
+/- consolidation (non-HCT candidates)
300 mg orally daily for 14 d of 28-d
treatment cycles (QUAZAR study)Oral
azacitidine17,18
Epigenetic
modification
(novel oral
formulation
of HMA)
q Preliminary data from the ongoing phase 3 SIERRA
trial confirm the feasibility of targeted conditioning with
Iomab-B with near-universal and rapid engraftment of
older patients with active AML and high BM blast burden
q No nonrelapse mortality reported in the Iomab-B arm;
select nonhematologic AEs included stomatitis,
malnutrition, and epistaxis, among others
q In phase 3 testing, most common grade 3/4 AEs
included neutropenia, thrombocytopenia, and anemia

3. Access the activity,“The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant,”
at PeerView.com/WRR40
Management of HCT-Eligible AML Patients
Induction, Post-Induction, and Post-Remission Therapya
PRACTICE AID
≥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 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 (FLT3-mutated AMLb
)
• Liposomal encapsulation of cytarabine and daunorubicin for therapy-related AML or
patients with antecedent MDS/CMML or AML-MRC
• 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
• Venetoclax + cytarabine
• 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. a
For complete dosing information, consult product labels and NCCN guidelines. b
FLT3-mutated ITD or TKD.
AML: acute myeloid leukemia; AML-MRC: acute myeloid leukemia with myelodysplasia-related changes; APL: acute promyelocytic leukemia; BSC: best supportive care; CBF: core-binding factor; CD: cluster of differentiation; CMML: chronic myelomonocytic leukemia; CPX-351: cytarabine:daunorubicin;
FLT3: fms-like tyrosine kinase 3; G-CSF: granulocyte colony-stimulating factor; HCT: hematopoietic cell transplantation; HMAs: hypomethylating agents; IDH2: isocitrate dehydrogenase 2; ITD: internal tandem duplication; MDS: myelodysplastic syndrome; PS: performance status; TKD: tyrosine
kinase domain.
1. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Acute Myeloid Leukemia. Version 3.2020. https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf. Accessed January 29, 2020. 2. Agura E et al. 2019 Transplantation and Cellular Therapy Meetings
(TCT 2019). Abstract LBA3. 3. Roboz GJ et al. Future Oncol. 2016;12:293-302.
Access the activity,“The Continuing Wave of Innovation in AML: Getting the Most From the Convergence of Novel Therapy and Allogeneic Transplant,”
at PeerView.com/WRR40
Management of HCT-Eligible AML Patients
Induction, Post-Induction, and Post-Remission Therapya
PRACTICE AID
≥60 Years of Age1
<60 Years of Age1
• BSC
Post-Remission(Consolidation)Therapy
Previous
Intensive
Therapy
Yes
Yes
No
No
Response?
Previous
Low-Intensity
Therapy
• Allogeneic 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 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
• Low-intensity therapy (azacitidine, decitabine)
• Matched sibling/alternative donor HCT
• High-dose cytarabine
• High-dose cytarabine and midostaurin (FLT3-mutated AML)
• Liposomal encapsulation of cytarabine and daunorubicin
for therapy-related AML other than CBF/APL, or patients with
antecedent MDS/CMML, or cytogenetic changes consistent
with MDS
Poor-Risk
Cytogenetics/
Molecular
Abnormalities
Treatment-
Related
DiseaseOr
Complete
Response? CBF
Translocations
• High-dose cytarabine ± gemtuzumab ozogamicin
(CD33-positive)
• 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
• Allogeneic 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
• Continue venetoclax + azacitidine
• Continue azacitidine or decitabine + sorafenib