ASCO 2024: Do Shorter Cycles of Venetoclax + HMA Benefit Frail AML Patients?

AML specialist Dr. Alexandre Bazinet from MD Anderson Cancer Center in Houston, TX, shared findings at the ASCO 2024 conference in June about the benefits AML patients who are elderly or too weak to qualify for intensive chemotherapy may receive from shortening the venetoclax + hypomethylating agent (HMA) treatment cycle. Read a summary of the key findings below. 

What is Venetoclax + HMA Therapy? 

Venetoclax (Venclexta) is a non-chemotherapy medicine given in the form of a pill. It targets cancerous AML cells by blocking the BCL-2 protein, which regulates cell survival and death. Overproduction of BCL-2 is common in cancer cells, and blocking it with venetoclax causes the cancer cells to die. 

Hypomethylating agents (HMA) like azacitidine (Vidaza or Onureg) and decitabine (Dacogen) work to kill AML cells by re-activating parts of the cancer cell’s genetic instructions (DNA) that tell the cell to self-destruct. These DNA parts in the cancer cell were previously silenced when they shouldn’t have been. 

Newly diagnosed AML patients who have medical conditions that prevent the use of intensive chemotherapy are approved by the FDA to take venetoclax in combination with a hypomethylating agent.  

What Happens if Venetoclax + HMA Treatment Cycles are Shortened? 

AML patients are usually advised to take venetoclax every day during the month and the HMA, like oral azacitidine, during the first two weeks. Each 28-day period, roughly one month, represents one treatment cycle. The medication administration rules restart with each cycle. 

AML specialists wanted to review if treating AML for only seven days with an HMA followed by seven days of venetoclax during each cycle would benefit patients instead of the more extended treatment period. 

Dr. Bazinet and his colleagues’ study results found the following about shortening venetoclax + HMA treatment cycles: 

• It was safe 
• It decreased patients’ needs for platelet transfusions 
• It decreased the risk of death at eight weeks from the start of treatment 
• It increased the rate of patients achieving MRD negativity, a highly sensitive clinical test that shows little to no cancer cells left in the bone marrow 
• Both patient groups experienced a similar complete reduction of AML signs and symptoms following treatment 
• Patients with TP53 mutated AML did not benefit 
• Patients with FLT3-ITD and N/KRAS AML had some benefit 
• Excluding TP53, FLT3-ITD, and N/KRAS AML, other types of AML had a high benefit 
• It reduced patients’ need for antifungal treatment 

In conclusion, Dr. Bazinet’s study shows several benefits of shortening venetoclax + HMA cycles for frail AML patients. Further studies will help assess the effectiveness of this treatment administration method. 

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Sources

• A retrospective comparison of abbreviated course “7+7” vs standard hypomethylating agent plus venetoclax doublets in older/unfit patients with newly diagnosed acute myeloid leukemia.
• Onureg Dosing Administration
• Venclexta for AML