Acute Myeloid Leukemia: What’s New on the Horizon?Interim Outcomes Report (as of August 17, 2020)

Jazz Pharmaceuticals Grant

Activity Description: This on-demand activity, featuring renowned faculty Naval Daver, MD from the University of Texas MD Anderson Cancer Center, was recorded at a live national visiting lecture series program reviewing the latest clinical trial data and introducing strategies for integrating novel treatments into precision medicine. In addition to the educational content, this activity offers downloadable resources and slides to improve care for clinicians who manage patients with AML.

Launch Date: April 22, 2020Expiration Date: April 22, 2021

Credit: 1.0 AMA PRA Category 1 CreditsTM

Sponsor: The University of Texas MD Anderson Cancer CenterEducational Partner: The Academy for Continued Healthcare Learning (ACHL) Supported by: An educational grant from Jazz Pharmaceuticals, Inc.

Intended Audience: Hematologists, oncologists and other healthcare professionals involved in the care of patients with AML such as pharmacists, oncology nurses, nurse practitioners, physician assistants.

Activity Availability: myCME.com: https://www.mycme.com/courses/acute-myeloid-leukemia-whats-new-on-the-horizon-7046 ACHLcme.org: https://www.achlcme.org/AMLwhatsnewonthehorizon Direct access: https://www.achlcme.org/digital/AMLVPP/index.html

Overview

Activity Screenshots

Executive SummaryParticipants

(as of 8/17/20)Certificates

(as of 8/17/20)

499 132

Predominant Audience: • 47% MDs, NPs and PAs• 34% Hem/Onc specialty

88% of hematology/oncology learners reported being likely to use CPX-351 for newly diagnosed patients over 60 years of age with high-

risk t-AML. This is a 78% relative increase over baseline likelihood.73% overall increase in

knowledge and competence

Learning Gains

Review and emphasize treatment strategies based on the most current clinical practice guidelines, up-to-date clinical trial findings and FDA approvals of personalized approaches for patients with newly diagnosed acute myeloid leukemia (AML)

Evaluate and examine recent drug approvals and evidence-based regimens for specific patients with relapsed or refractory AML, including toxicity management

Consider the prognostic implications of molecular and cytogenetic features of AML for disease diagnosis and relapse, and discuss application to selection of new targeted therapies such as FLT3- and IDH-inhibitors

Summarize advances in novel and investigational therapies for appropriate patient types with AML and analyze key clinical trial information about agents in late‐stage development including mechanism of action, safety and efficacy

58%35%

58%33%

Pre 1st Attempt Post

45% will provide more personalized care

38% will implement cytogenetic and mutational profiling

27% will personalize tx based on type for newly diagnosed pts

92% of learners will change their practice following participation in this activity

70% of learners discuss the option of enrolling eligible

patients in clinical trials for AML

49%27%

54%32%

82% of hematology/oncology learners demonstrated improved competence in selecting appropriate therapy (CPX-351) for a

hypothetical patient with t-AML post-activity.

Outcomes Reporting Methodology• First-attempt posttest scores are reported throughout:

• Initial answer choices for the posttest provide insight into the learners’ ability to immediately recall and apply the education.

• For post-activity questions administered as part of the evaluation (versus the online survey), only first-attempt was collected.

• Pre- and posttest responses have been paired/matched. Non-completer data has been omitted from the analysis to ensure comparison groups are equivalent.

Terminology Defined:• Participant: term used to describe an HCP who reviewed CME front matter and

took action to begin the education.• Hematology/Oncology learner: self-identified physician, nurse practitioner, or

physician assistant specializing in hematology or oncology who consumed the education.

Participation

15%

23%

9%24%

5%

9%

15%

Participation by Clinician Type

Physician

Physician Assistant

Nurse Practitioner

Nurse

Pharmacist

Student

Other HCP

Participants(as of 8/17/20)

Certificates (as of 8/17/20)

499 132

34%

11%7%7%

5%

5%

5%

26%

Participation by Specialty

Hematology/Oncology

Family Medicine/General Practice

Critical Care/Emergency Medicine

Orthopedics

Internal Medicine

Pharmacy

Pediatrics

Other

Learning ObjectivesPlease rate the following objectives to indicate if you are better able to: Analysis of Respondents

Rating scale: 4=Strongly Agree;

1=Strongly Disagree

LO1Review and emphasize treatment strategies based on the most current clinical practice guidelines, up-to-date clinical trial findings and FDA approvals of personalized approaches for patients with newly diagnosed acute myeloid leukemia (AML)

3.52

LO2 Evaluate and examine recent drug approvals and evidence-based regimens for specific patients with relapsed or refractory AML, including toxicity management 3.46

LO3Consider the prognostic implications of molecular and cytogenetic features of AML for disease diagnosis and relapse, and discuss application to selection of new targeted therapies such as FLT3- and IDH- inhibitors

3.46

LO4Summarize advances in novel and investigational therapies for appropriate patient types with AML and analyze key clinical trial information about agents in late‐stage development including mechanism of action, safety and efficacy

3.48

N=130

96% of learners strongly agree or agree that all learning objectives were met, with an average rating of 3.48.

Overall Evaluation

N=130

Please evaluate the following criteria: Analysis of RespondentsRating scale: 4=Excellent; 1=Poor

The presenters’ ability to effectively convey the subject matter 3.58

The effectiveness of the self-directed format: 3.58

78% confirm this

education will increase their competence

76% attest the content was relevant to their practice

70% discuss the option of enrolling eligible patients in clinical

trials for AML

71% report this activity will improve their patient outcomes

74% report education

received from this activity will

increase their performance

Self-reported attestations:

Objectivity & Balance

Activity was perceived as objective, balanced, and non-biased.

92%

8%

This activity was free of commercial bias:

Yes No

64%

33%

3%0%

10%

20%

30%

40%

50%

60%

70%

Excellent Good Fair Poor

Rating of objectivity & balance

N=130

Pretest vs. Posttest Summary

Participants demonstrated improved knowledge and competence across all three domains, however

continued education and reinforcement is necessary to maintain these gains and apply to clinical practice.

Topic % Change*

1 Selection of Therapy 76%

2 Application of Testing 61%

3 Treatment of Relapsed AML 81%

Overview of Correct Responses (Aggregate Learners)

*Relative percent change between pre-assessment score and 1st attempt post-assessment score.

73% Average Increase

58% 58%

49%

33% 36%27%

Pretest vs. Posttest Summary (cont)

38%48%

41%

69%76%

69%

0%

20%

40%

60%

80%

100%

Topic 1 Topic 2 Topic 3

Pre 1st Attempt Post

TopicHematology & Oncology Learners

% ChangePre vs 1st Attempt Post

Selection of Therapy 82%

Application of Testing 58%

Treatment of Relapsed AML 68%

Overview of Correct Responses (by Target Audience)

31% 31%21%

52% 49%40%

0%

20%

40%

60%

80%

100%

Topic 1 Topic 2 Topic 3

Pre 1st Attempt Post

Hematology/Oncology Learners

Other HCP Learners

TopicOther HCP Learners

% ChangePre vs 1st Attempt Post

Selection of Therapy 68%

Application of Testing 58%

Treatment of Relapsed AML 90%

Cohen’s d Effect Size: Aggregate Learners

An effect size of 0.66 indicates that learners are now ~41.08% more knowledgeable of the content assessed than prior to participating in this education.

Pretest Posttest

32%Mean

0.305Standard Deviation

132Sample Size

55%Mean

0.380Standard Deviation

132Sample Size

Cohen’s d Effect Size = 0.66

This Effect Size calculation includes all learner completers and encompasses all pre/post-test questions. First-attempt posttest and paired data were used to calculate post-test mean and standard deviation.

Cohen (1988): .2 = small, .5 = medium, .8 = largeWolf (1986): .25 = educationally significant, .50 = clinically significant

Clinical Confidence: Tx Selection

Interestingly, baseline confidence in the selection of therapy for newly diagnosed AML patients was lower in hem/onc learners. Nonetheless, both groups of learners reported an increase in

confidence after their participation.

How confident are you in selecting appropriate therapy for a patient with newly diagnosed treatment-related AML based on patient and disease characteristics?

A. Very confident

B. Somewhat confident

C. Not at all confident

Clinical Confidence: Therapy Selection

12%

57%

31%39%

56%

5%

A B C0%

20%

40%

60%

80%

100%

Pre (n=42) Post (n=42)

Hematology/Oncology Learners

Other HCP Learners

20%

46%34%38%

54%

8%

A B C0%

20%

40%

60%

80%

100%

Pre (n=90) Post (n=90)

Clinical Frequency: Tx Selection

Prior to their participation in the activity, 35-38% of learners reported not being familiar with CPX-351 or its available data;

marked improvements were observed postactivity. Both learner types also reported being more likely to use CPX-351 in this clinical

scenario after their participation, with more hem/onc learners reporting being “very” likely to use CPX-351 in this situation.

How likely are you to select CPX-351 (Liposomal Cytarabine and Daunorubicin) vs. standard-of-care cytarabine plus daunorubicin chemotherapy for a newly diagnosed patient over 60 years of age with high-risk therapy-related AML (t-AML)?

A. Very likely

B. Somewhat likely

C. Not at all likely

D. I am not aware of CPX or the data with this agent

Clinical Frequency: Therapy Selection

14%

36%

12%

38%44% 44%

5% 7%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=42) Post (n=42)

Hematology/Oncology Learners

Other HCP Learners

17%

34%

13%

36%31%

50%

14%5%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=90) Post (n=90)

Clinical Competence: Selection of Tx for t-AML

The percentage of learners selecting the most appropriate therapy for this hypothetical patient with t-AML increased 82% and 68% postactivity, in hem/onc and other learner

types, respectively. This increased competence correlates with the changes in familiarity with CPX-351 as reported on slide 14. Most learners accurately recognized that

gemtuzumab ozogamicin and enasidenib would not be options without molecular testing. However, approximately one-third of learners (25-30%) selected the less intensive

induction regimen of venetoclax+LDAC postactivity despite the absence of patient and clinical features that might require that approach. These data suggest that learners may

not be familiar with the indications for newer AML therapies.

A 62-year-old man was diagnosed with stage II gastric cancer, received surgical treatment followed by chemotherapy with 5-FU and radiation therapy 4 years prior and has remained disease-free since that time. He works as a plumber and has no other comorbidities. He is admitted from the clinic for fatigue, shortness of breath and abnormal blood counts. His peripheral smear showed white blood cell (WBC) count of 12.6x109/L, hemoglobin 8.5 and thrombocyte count of 21x109/L. Bone marrow test showed 86% blast count. He was diagnosed with t-AML, mutational studies were sent and will take 12 days to come back. Which of the following would be the best treatment for this patient?

A. Venetoclax + low dose cytarabine (LDAC)

B. CPX-351

C. Gemtuzumab ozogamicin as a single agent

D. Enasidenib as a single agent

Learning objectives: Review treatment strategies for patients with newly diagnosed AML (LO1) and summarize investigational therapies (LO4)

48%38%

7% 7%

26%

69%

5%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=42) 1st Attempt Post (n=42)

Hematology/Oncology Learners

Other HCP Learners

30% 31% 34%

5%

30%

52%

15%3%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=90) 1st Attempt Post (n=90)

Clinical Competence: Application of Testing

Both learner types demonstrated a 58% increase in the accurate application of testing results and selection of therapy for this hypothetical newly diagnosed patient. Competency was higher in hem/onc learners, but a proportion of all learners continued to select an inappropriate therapy based on the patient’s

molecular and cytogenetic features, suggesting a need for continued education.

A 41- year old aerobic exercise trainer is in the clinic with complaints of excessive tiredness and shortness of breath. Her medical history is unremarkable. Her white blood cell (WBC) count is 40x109/L, platelet count is 24x109/L and bone marrow test shows 79% blasts. PCR testing and NGS revealed FLT3-ITD mutation, cytogenetics are diploid, additional broad mutational profiling is pending. For this patient with newly diagnosed AML, which of the following would be an appropriate treatment?

A. 7+3 chemotherapy [cytarabine + an anthracycline (daunorubicin or idarubicin)], plus venetoclax

B. 7+3 chemotherapy [cytarabine + an anthracycline (daunorubicin or idarubicin)], plus midostaurin

C. 7+3 chemotherapy [cytarabine + an anthracycline (daunorubicin or idarubicin)], plus gemtuzumab ozogamicin

D. 7+3 chemotherapy [cytarabine + an anthracycline (daunorubicin or idarubicin)], plus crenolanib

Learning objectives: Review treatment strategies for patients with newly diagnosed AML (LO1) and consider prognostic implications of molecular and cytogenetic features of AML (LO3)

17%

48%

28%

7%10%

76%

14%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=42) 1st Attempt Post (n=42)

Hematology/Oncology Learners

Other HCP Learners

25% 31% 33%

11%21%

49%

21%9%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=90) 1st Attempt Post (n=90)

Clinical Competence:

There were marked increases in the appropriate interpretation of the molecular and cytogenetic features reported for this patient with relapsed AML. Despite these gains, more than one-third of hem/onc learners and more than one-half of other learners continued to select inappropriate therapies based on the presence of a FLT3-ITD mutation. Education should continue to focus on the interpretation and application of testing results in the selection of therapy for diverse AML patients.

A 76-year-old man with AML received 3+7 induction followed by HiDAC x 2 cycles, but his symptoms did not improve. His current white blood cell (WBC) count was 37x109/L, platelets 42x109/L and bone marrow evaluation showed 78% blasts. PCR and NGS testing revealed FLT3-ITD mutation. Which treatment would be appropriate for this patient?

A. CPX-351

B. Midostaurin

C. Gilteritinib

D. Ivosidenib

Learning objectives: Evaluate recent drug approvals for relapsed or refractory AML (LO2) and consider prognostic implications of molecular and cytogenetic features of AML (LO3)

21% 24%

41%

14%17% 12%

69%

2%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=42) 1st Attempt Post (n=42)

Hematology/Oncology Learners

Other HCP Learners

36% 32%21%

11%21% 21%

40%

18%

A B C D0%

20%

40%

60%

80%

100%

Pre (n=90) 1st Attempt Post (n=90)

Practice Change

92% of learners will change their practice! Specifically, 45% intend to provide more personalized, patient-centered care and 38% will implement appropriate patient work-up including cytogenetic and mutational profiling.

8%

14%

18%

27%

31%

45%

38%

0% 10% 20% 30% 40% 50%

This activity validated my current practice; no changes will bemade

Other change

Create/revise protocols, policies, and/or procedures relating totreatment of therapy-related AML

Personalize therapy based on type of AML for my newly diagnosedAML patients

Integrate approved novel therapies for AML into my practice

Provide personalized, patient-centered care

Implement appropriate patient work-up including cytogenetic andmutational profiling

Post (n=130)

N=130; multiple responses allowed

Patient Care Impact

22%

44%

22%

7% 5%

Number of patients with AML seen per week:

0

1-5

6-10

11-20

>20

Changes in the interpretation of molecular and cytogenetic testing and application to selection of therapy made by hematology/oncology learners has the potential to impact 552 to more than 1064 patients with AML each week. This

assumes the data in the first chart above is representative of all hematology/oncology participants (170) who indicated they would change their practice as a result of their participation in this activity (89%).

N=41

49%

41%

7%2%1%

Number of patients with AML seen per week:

N=89

Hematology/Oncology Learners Other HCP Learners

Barriers to Planned Change

Participants indicated insurance/reimbursement issues (25%) as most common barrier to implementing changes in their practice, followed by cost (20%) and lack

equipment or necessary resources (19%). Of those who identified barriers, 86% will attempt to address the perceived barrier(s) in order to affect change.

N=130; multiple responses allowed

26%6%

8%5%

12%14%

17%18%

19%20%

25%

0% 5% 10% 15% 20% 25% 30%

No barriersOther

Lack of consensus or professional…Lack of supporting evidence in the literature

Organizational/institutional cultureDo not have an implementation strategy

Lack of staff time to implement changePatient adherence/compliance issues

Lack of equipment or necessary resourcesCost

Insurance/reimbursement issues

Topics of Interest

5%

15%

28%

36%

38%

44%

0% 20% 40% 60%

Other

Integrating MRD into clinical practice in AML

Novel therapies in AML

Patient education

Targeted therapies

Management of AML

The broad topic of management of AML was selected with the highest interest for future education. Considerate of the additional topics of interest, the recommendation is for the development of additional education that would

continue to address the new and emerging data, the role of testing, implications for treatment, and treatment selection.

N=130

Other

Implications for the Future• Findings from this activity support continued education focusing on the

selection of therapy• Continued reinforcement of CPX-351 clinical application and recent and

emerging efficacy and safety data• Case-based education with interactivity, decision trees, and learner

feedback to improve competency and application to practice• Expand education to managed care pharmacists, hospital pharmacists,

and payers to inform on the safety and efficacy of recently approved agents

Contact InformationAmanda Kaczerski, MS, CHCPVP, Education DevelopmentAcademy for Continued Healthcare Learning (ACHL)

E: akczerski@achlcme.orgP: 773-714-0705 ext. 148C: 973-495-4828