Venclexta combination improves survival and lowers hospital stays for AML patients | ASH 2025

The combination of azacitidine and Venclexta (venetoclax) led to better responses and improved event-free survival in patients who were fit enough to undergo standard-of-care chemotherapy for newly diagnosed patients with acute myeloid leukemia (AML). The results suggest the combination can lead to better outcomes with substantially less hospitalization and a lower symptom burden for patients with intermediate-to-high-risk disease, according to a new study presented today at the 67th American Society of Hematology (ASH) Annual Meeting being held in Orlando.

AML is a rare blood cancer that begins in the bone marrow. It leads to abnormal white blood cells and hinders the production of healthy blood cells. Hematopoietic stem cell transplantation can cure AML, but this option is not available to everyone. Patients who are eligible for a transplant have to have an induction course of chemotherapy to reduce the cancer in the bone marrow. This requires time in the hospital and carries a high risk of infection, bleeding, and other complications.

In 2025, about 22,000 people in the United States will be diagnosed with AML, and about 11,000 Americans will die from the disease, according to the American Cancer Society.

“For over five decades, the standard upfront treatment for functionally fit patients with AML has been intensive induction chemotherapy, incorporating cytarabine and various anthracyclines,” Amir T. Fathi, M.D., associate professor of medicine, Harvard Medical School, and program director, Center for Leukemia, Massachusetts General Hospital, said during a press brief today. “Despite advances for certain AML subsets, intensive chemotherapy continues to yield suboptimal outcomes for most of our patients. Unfortunately, intensive induction chemotherapy comes with substantial burden and costs.”

He said that intensive induction chemotherapy is associated with significant morbidity, including narrow circulation, frequent infections and breathing complications, malnutrition, deleterious psychosocial effects and increased risk of cardiac injury and secondary malignancies.

The combination of azacitidine and Venclexta has been used when patients are not well enough for the standard regimen of chemotherapy. Azacitidine is an injectable chemotherapy drug that is used for older patients with AML. Venclexta is an oral targeted therapy that inhibits the BCL-2 protein, which is involved in cancer cell survival.

In this phase 2 trial, investigators enrolled 172 adult patients between the ages of 23 and 79. They were randomly assigned to receive either the combination of azacitidine/Venclexta or standard induction chemotherapy. The standard treatment was either the combination of liposomal daunorubicin and cytarabine or the 7+3 regimen, which is cytarabine plus anthracycline.

Fathi explained that people with FLT3 mutations were excluded because investigators did not want to randomize patients that were not included in the trials for the approved indication of Vencexta. Developed by AbbVie and Genentech, Venclexta is approved for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma, as well as for adults 75 years or older with newly diagnosed acute myeloid leukemia (AML) in combination with azacitidine, decitabine, or low-dose cytarabine.

Although this was an investigator-initiated trial, it was funded by the pharmaceutical companies. The primary endpoint of this study was event-free survival, and events were defined as progressive disease or persistent disease requiring a therapeutic change, relapse, transition to hospice or death. Secondary endpoints included rates of disease response, overall survival, toxicity and adverse events, measurable residual disease cost analysis, healthcare utilization metrics and patient-reported outcomes.

Investigators found that with a median follow-up of just under 22 months, event-free survival was significantly longer in the azacitidine/Venclexta arm; the median event-free survival was more than 14 months among those receiving azacitidine/Venclexta compared with a median of just over 6 months for those receiving induction chemotherapy.

Patients who received azacitidine/Venclexta experienced a higher overall response to treatment than those receiving induction chemotherapy, with 88% of those in the azacitidine/Venclexta arm seeing an overall response and 78% seeing a composite complete response, compared with 62% and 54% in the control arm, respectively. They were also more likely to progress to a transplant, which occurred in 61% of those receiving azacitidine/Venclexta and 40% of those receiving induction chemotherapy.

The rate of grade 3 or 4 therapy-related adverse events was similar between study arms. No patients who received azacitidine/Venclexta died within 60 days, while 5% of those in the control group died by this timepoint. Hospitalization was also longer among patients in the control group.

“We believe these data support the use of azacitidine and venetoclax for functionally fit patients eligible for transplant with intermediate or adverse risk,” Fathi said.

Researchers plan to conduct further analyses to compare costs, the rate of infectious complications, and other factors that may inform treatment decisions for this patient population.