What Works Better for AML: Intensive Chemotherapy or Venetoclax/HMAs?

For older patients over the age of 75 or those who can’t receive intensive chemotherapy, the combination of venetoclax with a hypomethylating agent (Ven/HMA) offers a highly effective alternative. However, the long-term curative potential of this regimen remains uncertain. 

Dr. Andrew Zale, resident at The  Johns Hopkins Hospital, shared the findings of a retrospective study at the 66th annual ASH conference. This study focused on NPM1-mutated AML patients without FLT3-ITD mutations, and theorized that their AML can be cured with intensive chemotherapy alone. 

A retrospective analysis compared overall survival (OS) between patients with favorable-risk NPM1-mutated AML treated with either intensive chemotherapy or venetoclax combined with a hypomethylating agent. The study analyzed 55 patients, aged 60 to 75, from the Johns Hopkins institutional database and used advanced statistical methods to evaluate survival outcomes and contributing factors.

Key Study Findings

• Patients treated with intensive chemotherapy were younger and more likely to have undergone treatment before the FDA approved venetoclax
• A higher proportion of patients, 69%, underwent transplantation at first remission 
• Response and Survival Outcomes: Response rates were similar between the two groups. Median overall survival was 6.2 years for the intensive chemotherapy group compared to 4.9 years for the Ven/HMA group. 
• Factors Influencing Survival:
  • Higher baseline white blood cell counts were associated with worse survival outcomes
  • Transplantation in first remission significantly improved survival

Among Ven/HMA-treated patients who underwent transplantation (37%), survival outcomes were excellent. None experienced a relapse, and only one patient passed due to non-relapse causes. 

Takeaway Message

For patients aged 60 to 75 with favorable-risk NPM1-mutated AML, both intensive chemotherapy and venetoclax/hypomethylating agents can offer comparable responses, which can lead to eligibility for stem cell transplant and ultimately, comparable survival outcomes. Choosing between these therapies depends on the patient’s characteristics and individual preferences.

This analysis emphasizes the importance of tailoring treatment decisions to the unique circumstances of each patient. It also highlights the need for alternative therapy options that further improve outcomes, as well as next-generation sequencing for measurable residual disease testing. These findings provide valuable guidance for patients and caregivers navigating treatment options and underscore the evolving landscape of AML management.

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