Blood Cancer Talks

Episode 51. Venetoclax in AML with Dr. Andrew Wei

Sep 27, 2024

Dr. Andrew Wei, a leading expert in acute myeloid leukemia from the Peter McCallum Cancer Center, discusses the innovative use of venetoclax in treating AML. He highlights groundbreaking clinical trials that have transformed treatment pathways, particularly for older patients. Innovative therapies like venetoclax combined with hypomethylating agents are explored, along with ongoing resistance challenges and the role of genetic mutations in personalized treatment. The conversation also touches on the implications of minimal residual disease negativity in enhancing patient outcomes.

56:57

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Andrew Wei

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Quick takeaways

Venetoclax, in combination with hypomethylating agents, significantly improves overall survival in elderly AML patients compared to traditional chemotherapy.

Understanding the resistance mechanisms of AML cells highlights the importance of combining venetoclax with other treatments for optimal therapeutic outcomes.

Deep dives

Professor Andrew Vee's Journey in AML Research

Professor Andrew Vee's career trajectory in acute myeloid leukemia (AML) research is marked by a significant transition from clinical hematology to a focus on laboratory research in apoptosis. Initially set to pursue a clinical fellowship in hematology, he was introduced to the concept of research through an unexpected opportunity to undertake a PhD in apoptosis. His decision to remain in Australia and focus on AML came from a determination to address the lack of effective treatments for older patients suffering from this disease. Vee’s excitement grew upon the advent of venetoclax, a BH3 mimetic drug, as it provided a promising avenue to tackle AML, aligning closely with his research expertise.

Intro

4min

Elderly AML: Case Study and Treatment Innovations

4min

Understanding Apoptosis and Cancer Resistance Mechanisms

3min

Advancements in AML Treatment: Venetoclax and Azacitidine

24min

Exploring MRD Negativity in AML Treatment Decisions

4min

Venetoclax Resistance and Trials in AML

18min

In this episode, we discuss the history of venetoclax in AML, along with key clinical trials that have shaped its current use in AML. Here are the trials discussed in this episode:

1. VIALE-A study: https://www.nejm.org/doi/full/10.1056/NEJMoa2012971

2. 10 day Decitabine plus venetoclax for ND AML https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(20)30210-6/abstract

3. Genetic Risk Stratification and Outcomes with AML treated with venetoclax and azacitidine https://ashpublications-org.proxy.library.vanderbilt.edu/blood/article/doi/10.1182/blood.2024024944/517355/Genetic-Risk-Stratification-and-Outcomes-Among

4. Genetic risk classification for adults with AML receiving less-intensive therapies: the 2024 ELN recommendations https://ashpublications-org.proxy.library.vanderbilt.edu/blood/article/doi/10.1182/blood.2024025409/517356/Genetic-risk-classification-for-adults-with-AML

5. AGILE study: Ivosidenib and azacitidine in IDH1-mutated AML https://www.nejm.org/doi/full/10.1056/NEJMoa2117344

6. MRD response and prognosis in treatment naïve AML with AZA/VEN https://ascopubs.org/doi/10.1200/JCO.21.01546?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

7. Monocytic subclone confer resistance to venetoclax-based therapy in patients with AML https://aacrjournals.org/cancerdiscovery/article/10/4/536/2403/Monocytic-Subclones-Confer-Resistance-to

8. VEN/DEC vs 7+3 https://ashpublications.org/blood/article/142/Supplement%201/970/503790/Comparing-the-Efficacy-and-Safety-of-Venetoclax

9. FILO study: Outcomes of AML https://onlinelibrary.wiley.com/doi/10.1002/ajh.27417

10. Treatment-free remission after ceasing venetoclax-based therapy in patients with AML https://ashpublications-org.proxy.library.vanderbilt.edu/bloodadvances/article/6/13/3879/485175/Treatment-free-remission-after-ceasing-venetoclax

11. Targeting molecular MRD and low-blast relapse in AML with Venetoclax and LDAC (VALDAC) https://ascopubs-org.proxy.library.vanderbilt.edu/doi/10.1200/JCO.23.01599?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

12. INTERCEPT trial: https://ashpublications.org/blood/article/140/Supplement%201/3341/492722/ALLG-AMLM26-Phase-1B-2-Study-Investigating-Novel