New results from Blood Cancer United’s Beat AML Master Clinical Trial published by Borate et al in the journal Blood provide new information about whether older patients with newly diagnosed acute myeloid leukemia (AML) can receive a shorter schedule of venetoclax when it is given in combination with azacitidine.
The OPTI-AML study found that a 14-day venetoclax schedule did not meet criteria to show it performed similarly to the standard 28-day schedule based on complete remission rates. The findings also suggest that the optimal duration of venetoclax may vary by AML genetic mutation, reinforcing the need to tailor treatment based on disease biology.
Azacitidine plus venetoclax is standard treatment for older patients with newly diagnosed AML who are not eligible for intensive chemotherapy. While effective, the treatment can cause prolonged low blood counts, which may increase risk of infection and lead to treatment delays. In clinical practice, the duration of venetoclax is often reduced to 14 to 21 days to help patients recover blood counts, but evidence comparing shorter schedules has been limited and has not yet included a randomized trial.
“The perception in the blood cancer community is that 28 days of venetoclax for two cycles is too toxic—it causes low counts, dose delays, and ultimately, clinicians may shorten the schedule,” explained lead author Uma Borate, MBBS, of The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) in Columbus. “Our study shows that shortening treatment to 14 days is not a one-size-fits-all solution for older patients with AML.”
More on OPTI-AML
OPTI-AML, a sub-study of Beat AML, compared the standard 28-day venetoclax schedule with a 14-day schedule, both given with standard doses of azacitidine for two cycles. The study enrolled 169 patients aged 60 years and older with newly diagnosed AML who were not eligible for intensive chemotherapy.
The study’s primary endpoint was complete remission achieved at any time during the first two cycles of therapy. Complete remission rates were 49.4% for the 28-day schedule compared with 43% for the 14-day schedule. The 14-day schedule did not meet the study’s prespecified criteria for noninferiority.
Findings also varied by genetic mutation. Patients with NPM1 or IDH2 mutations had higher complete remission rates with the 28-day schedule compared with the 14-day schedule, while patients without those mutations had comparable complete remission rates between the two arms.
The results reinforce that AML is not a single disease, but many different diseases that may require treatment approaches tailored to disease biology.
“As Beat AML nears its 10-year milestone, this study shows how the trial continues to answer questions that matter in real-world care,” said Lore Gruenbaum, PhD, Chief Scientific Officer at Blood Cancer United. “We are not only looking for the next breakthrough—we are learning how to use today’s treatments more effectively, safely, and precisely for the patients most likely to benefit. These findings are an important reminder that reducing treatment intensity may help some patients, but it can also risk compromising response in others. Our goal is to generate the evidence clinicians need to make those decisions with greater confidence.”
The findings are especially important as researchers continue to study new triplet combinations that build on azacitidine and venetoclax. The study authors noted that future research should continue evaluating how venetoclax duration can be optimized for different genetic subgroups, particularly as new targeted therapies are added to AML treatment.
DISCLOSURE: For full disclosures of the study authors, visit ashpublications.org/blood.
