Increased understanding of the driving genetic and epigenetic factors of acute myeloid leukemia (AML) in recent years has helped to refine novel chemotherapy combinations in the frontline setting. Advances in the frontline treatment of AML, including both the optimization of chemotherapeutic approaches and emergence of targeted therapies, have led to better outcomes in specific genetic subsets of AML. Furthermore, risk stratification of patients with AML has allowed for personalized treatment decisions and improved outcomes.1
The ‘7+3’ regimen (7 days of cytarabine + 3 days of an anthracycline) is the predominant induction chemotherapy for young patients with newly diagnosed (ND) AML,2 but treatment options for elderly patients are more limited.3 Among the efforts being made to optimize frontline therapy are dose/schedule modifications of existing regimens. The aim here is to improve patient experience and limit the frequency of toxicities, all while maintaining efficacy. Changes to established regimens also require validation through clinical trials.
Despite advances in the frontline treatment options for patients with AML, challenges with treatment safety and efficacy persist. The AML Hub will be focusing on advances in frontline chemotherapy as an educational theme. In this introductory article, the AML Hub outlines the abstracts from the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition considered by our Steering Committee to be practice changing in this setting. These abstracts are summarized below, accompanied by expert commentary from leaders in the AML community.
Novel chemotherapy combinations
Venetoclax + FLAG-IDA as induction or consolidation therapy for patients with AML (#332)4
It has been suggested that the Bcl-2 inhibitor, venetoclax, might enhance the anti-leukemic activity of the combination regimen FLAG-IDA: fludarabine, cytarabine, granulocyte-colony stimulating factor, and idarubicin. At ASH 2020, Curtis Lachowiez presented the interim results of a phase Ib/II study of venetoclax in combination with FLAG-IDA for the treatment of patients with ND or relapsed/refractory AML.
In patients with ND AML, an overall response rate of 97% was observed, and the highest composite complete remission (CRc) rates were achieved in patients with ND AML (90%). MRD negativity was attained in 96% of patients when venetoclax + FLAG-IDA was employed in the frontline setting. Read the AML Hub summary for the full study design and safety and efficacy data.
Below you’ll find the thoughts of some of our Steering Committee members, as well as a video interview with Curtis Lachowiez in which we asked, What patients benefit most from the addition of venetoclax to FLAG-IDA?