Emerging Trends in Frontline Treatment for Acute Myeloid Leukemia (AML): A Survey of NCI-Designated Cancer Centers

Introduction:

For the past several decades the standard of care treatment for frontline therapy for acute myeloid leukemia (AML) in individuals that are eligible for intensive induction therapy has been 7 + 3 (7 days of cytarabine (Ara-C) + 3 days of danuorubicin). Older individuals with AML and those that are ineligible for intensive induction tend to be a more difficult population to treat. Since 2018, venetoclax + hypomethylating agents (HMA) (azacitidine or decitabine) has been considered the standard of care frontline treatment for AML in those who are induction ineligible. Over the past decade there have been significant improvements in genetic and molecular testing that have greatly impacted the development of new frontline treatment therapies for individuals with acute myeloid leukemia (AML) with promising treatment outcomes.

Methods:

In an effort to quantify the impact that these evolving therapies have had on influencing leukemia treatment practices, a questionnaire was sent to every director/chair of Leukemia at each National Cancer Institute (NCI) designated center. Our two-question questionnaire centered around determining the preferred AML treatment for both patients who are not on clinical trials that are eligible and those that are ineligible for intensive induction therapy. Questions were created based on the 2019 NCCN clinical practice guidelines for AML. The survey was limited to 2 questions so as to elicit higher response rate to the questionnaire.

Question #1:

What is the preferred induction regimen backbone used at your center -

In patients eligible for intense chemo, off-study?

• 7+3

• FLAG-IDA

• CLAG-IDA

• Venetoclax w/ 5-azacytidine or decitabine

• Other

Question #2:

What is the preferred induction regimen backbone at your center -

In patients who are ineligible for intensive chemo, off-study, and having actionable mutations (IDH or FLT3)?

• Venetoclax + Hypomethylating agent

• Targeted agent against IDH or FLT3 withoutvenetoclax +/- hypomethylating agent

• Targeted agent against IDH or FLT3 withvenetoclax +/- hypomethylating agent

• Other

Results:

From our study, we received 31/63 (49.2%) responses and saw that for the intensive induction 90.3% (28/31) respondents selected 7 +3 as the preferred treatment with 3.2% (1/31) choosing FLAG-IDA, with the remaining 6.5% (2/31) choosing “other” ((7 +3) w/ FLT3 inhibitor). Comparatively, for the intensive induction ineligible treatment, 61.3% (19/31) respondents preferred venetoclax + HMAs with 38.7% (12/31) preferring targeted agent w/ venetoclax +/- HMA. Of note, four respondents selected venetoclax + HMA as the preferred treatment, but also preferred aza-ivosidenib for IDH1 mutant AML.

Conclusion:

Preliminary findings from our survey suggest that results from genetic molecular testing may have a greater influence on the evolution in treatment for the intensive induction ineligible population. As more data comes out regarding combining targeted therapy with more broad-based treatments, clarity will emerge on the most appropriate standard-of-care approach. Additionally, improved turnaround time of testing methodology will likely modify treatment approaches. Our next steps include repeat outreach to obtain 100% response rate and sending a follow-up questionnaire to understand the rational for each specific treatment choice.