In a recent clinical trial, patients with newly diagnosed acute myeloid leukemia (AML) achieved better outcomes when treated with a combination of azacitidine and venetoclax, known as aza-ven, compared to those receiving standard induction chemotherapy. The study is the first to directly compare the efficacy of aza-ven to intensive induction chemotherapy, which has been the primary treatment for fit AML patients.
AML is a cancer that affects bone marrow and disrupts the production of healthy blood cells. While hematopoietic stem cell transplantation can cure AML in some cases, most patients need initial therapy to reduce cancer cells before considering transplantation. Standard induction chemotherapy typically involves cytarabine and anthracyclines and requires extended hospitalization along with risks such as infection and bleeding.
Azacitidine has long been used in injectable form for older AML patients, while venetoclax is an oral medication targeting the BCL-2 protein. These drugs are generally well tolerated and can be administered on an outpatient basis.
The trial included 172 adults randomly assigned to receive either aza-ven or standard intensive chemotherapy. The main outcome measured was event-free survival (EFS), which considers relapse, disease progression, therapy change due to refractoriness, or death as events. With a median follow-up of just under 22 months, those treated with aza-ven had a median EFS exceeding 14 months versus just over six months for those on standard chemotherapy. At one year, 53% of aza-ven recipients remained event-free compared to 36% in the control group.
Certain patient groups—those with core binding factor fusions, FLT3 mutations, or NPM1 mutations (unless aged 60 or above)—were excluded from this study. This means the results mainly apply to intermediate-to-high-risk AML patients who are eligible for intensive treatment.
"I believe the data support the use of this treatment in this population," said Dr. Fathi. "It applies to adverse risk and intermediate risk patients who don't have FLT3 mutations. That doesn't mean that other patient populations may not benefit, but they require their own focused study."
Patients given aza-ven showed higher overall response rates: 88% had an overall response and 78% achieved composite complete response compared to 62% and 54%, respectively, among those on induction chemotherapy. More participants in the aza-ven arm were able to proceed to transplant—61% versus 40%.
Serious side effects were similar between both groups; however, none of the patients receiving aza-ven died within 60 days while there was a 5% mortality rate at this point among controls. Hospital stays were longer for those undergoing induction chemotherapy; additionally, ICU admissions occurred only among these patients (10%) and not among those treated with aza-ven. Quality-of-life assessments also favored the aza-ven group regarding symptom burden and depression at two weeks.
Researchers plan further analysis focusing on costs and infectious complications related to each regimen as well as studying measurable residual disease status across both arms of treatment.
The investigator-led study received drug supply and research staff funding from Genentech and AbbVie Inc., manufacturer of venetoclax.
Amir Fathi, MD from Mass General Brigham Cancer Institute and Harvard Medical School will present these findings during a plenary session at West Hall D2 of Orange County Convention Center on Sunday December 7th at 3:45 p.m Eastern time.
