Dr. Gabriel Mannis, an AML expert from Stanford University in California discusses the work he presented at the annual ASH meeting on a new oral version of the hypomethylating agent decitabine in combination with the oral BCL-2 inhibitor venetoclax. 

Dr. Mannis states that for the past 3 years, the standard of care for treating older patients with AML has been the combination of venetoclax with a hypomethylating agent, either decitabine or azacitidine that is given either intravenously (IV) or as injections under the skin. Dr. Mannis’s study is the first trial of an all oral regimen to treat newly diagnosed older AML patients. This trial was a phase 1 study meaning that this is the first time this combination has been studied in humans. Both venetoclax and oral decitabine are both FDA-approved drugs but have never been studied in combination. This research is exciting for patients because it has the potential to shift the way AML is treated in older adults. 

Currently, IV or injected decitabine or azacitidne is given every month as long as it is working. Patients must come into cancer center or infusion clinic for 5-7 days in a row every month to get their IV infusions or injections, and so if these IV treatments are able to be provided instead as pill treatments, it will really improve the quality of life for patients with AML.

In this phase 1 study, Dr. Mannis and his colleagues report the findings of the first 25 patients enrolled. The primary objective of this study was to make sure the combination is safe and that there aren’t any unexpected side effects relative to the IV version of decitabine. 

First, the researchers found that there were no side effects that were different or unexpected relative to the IV version of decitabine. Second, the researchers wanted to see if the oral decitabine was as effective as the IV version. Of 20 patients who were able to be evaluated for response, they saw complete remission in two-thirds of patients, which is very similar to what is seen in other studies looking at the use of IV decitabine in combination with venetoclax.

The bottom line is that in the phase 1 study it appears that the all oral combination of oral decitabine with venetoclax is safe and well tolerated and in a preliminary look it seems to be just as effective as the IV version.

As a result of this study, researchers have recently launched a phase 2 study in which they will enroll another 100 patients across the world expanding the study from 7 sites to sites throughout the United States and Europe. Based on this study, if the all oral combination continues to appear safe and effective, Dr. Mannis hopes that this treatment will soon become FDA approved and the new standard of care for treating older adults with AML.

To learn more about oral decitabine and Dr. Mannis's work, click here to listen to the podcast episode we did together on this topic back in Sept 2021.