The combination of azacitidine and venetoclax led to improved efficacy outcomes with fewer complications than standard intensive induction chemotherapy as upfront treatment for patients with acute myeloid leukemia (AML), according to trial findings presented at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 6).
“Our study met its primary endpoint, demonstrating that azacitidine/venetoclax improves event-free survival. It also leads to higher rates of overall response and composite complete response than intensive induction chemotherapy in younger, intensive-chemotherapy–eligible patients,” said lead study author Amir Fathi, MD, Director of the Center for Leukemia at Mass General Brigham Cancer Institute and Associate Professor of Medicine at Harvard Medical School in Boston, Massachusetts. “A greater proportion of patients successfully proceeded to transplant following response with less early mortality, significantly improved quality of life during initial treatment, and less time in the hospital.”
Background and Study Methods
Standard upfront therapy for fit patients with AML has typically been intensive induction chemotherapy, but outcomes have been poor long term and it is associated with significant complications and burden to patients and hospitals.
Researchers conducted an open-label, multicenter, randomized phase II trial to compare the efficacy of azacitidine in combination with venetoclax vs conventional induction and consolidation chemotherapy of 7+3 regimen or liposomal daunorubicin and cytarabine (CPX-351) in eligible adult patients with AML. Exclusion criteria included core binding factor fusions, FLT3 mutations, and NPM1 mutations, unless patients were 60 years or older. All patients were able to proceed to hematopoietic cell transplantation following response to therapy.
Key Findings
A total of 172 patients were enrolled across 9 centers in the United States. In the chemotherapy arm, 54% of patients received 7+3 and the remainder received CPX-351 for a median of two cycles; patients in the azacitidine/venetoclax arm received a median of four cycles.
The overall response rate in the azacitidine/venetoclax arm was 88% as compared with 62% in the intensive induction chemotherapy arm (P < .001); the clinical complete response rates were 81% and 55% in the doublet and chemotherapy arms (P < .001), respectively.
Rates of procession to transplantation were 61% in the azacitidine/venetoclax arm and 40% in the chemotherapy arm (P = .009).
At a median follow-up of 16 months, the event-free survival rate at 1 year was 53% in the azacitidine/venetoclax arm and 39% in the chemotherapy arm (hazard ratio = 0.61; P = .017). Overall survival data are continuing to mature.
“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.”
Common grade 3/4 therapy-related adverse events were mostly hematologic, and were reported at similar rates in both arms. Of note, grade 3/4 lung infections occurred in 12% of patients in the azacitidine/venetoclax arm and in 15% in the chemotherapy arm, and sepsis was reported in 7% in the doublet arm and in 11% in the standard therapy arm. Mortality rates at 30 and 60 days were 0% in the azacitidine/venetoclax arm as compared with 3.5% and 4.7% in the chemotherapy arm, respectively.
Patients in the doublet arm reported significantly better quality of life (P = .001), symptom burden (P= .019), and depression symptom (P = .007) scores at 2 weeks than patients in the standard induction chemotherapy arm. Additionally, patients in the azacitidine/venetoclax arm were less likely to be admitted to the ICU (0% vs 9.8%; P = .003) and experienced fewer inpatient days at initiation and during the first 6 months (P < .001) as compared with patients in the chemotherapy arm.
Disclosure: The study was investigator-initiated; Genentech and AbbVie provided the study drug and funding to support research staff. For full disclosures of the study authors, visit hematology.org.
