A multicenter real-world study reveals that venetoclax combined with hypomethylating agents achieves higher overall response and complete remission rates than intensive chemotherapy in newly diagnosed intermediate-risk acute myeloid leukemia patients, challenging long-standing treatment paradigms.
Standard AML Induction Therapy
Intensive induction chemotherapy has served as the upfront treatment for functionally fit patients diagnosed with acute myeloid leukemia. However, this aggressive approach routinely subjects patients to profound myelosuppression, severe infections, and hemorrhage while yielding suboptimal long-term survival outcomes across many patient subsets.
The medical community has increasingly questioned whether aggressive regimens remain appropriate for every demographic, particularly as targeted therapies emerge. Acute myeloid leukemia is an aggressive hematologic malignancy characterized by the abnormal proliferation of myeloblasts, which leads directly to bone marrow failure and rapid health decline if left untreated.
In the United States, the condition accounts for 31% of adult leukemia cases and predominantly impacts older adults, carrying a median diagnosis age of 68 years. In 2022, approximately 20,050 new cases were reported domestically. Meanwhile, European incidence rates hover around 3.5 per 100,000, with major nations registering thousands of diagnoses annually among aging populations.
“For a long time, we’ve had a dichotomous choice in AML treatments: either super heavy-duty induction chemotherapy, also known as 7+3, or less-intensive therapies like azacitidine,”
Aaron T. Gerds, MD, MS
Real-World Data From Hunan Tertiary Hospitals
A recent multicenter retrospective matched cohort analysis sheds new light on this clinical debate. Researchers evaluated 229 newly diagnosed non-acute promyelocytic leukemia patients classified as intermediate-risk under the 2022 European LeukemiaNet criteria. These individuals received treatment across four tertiary hospitals in China’s Hunan Province between January 2016 and February 2025.
Among the study cohort, 88 patients received a combination of venetoclax and hypomethylating agents, while 141 underwent intensive chemotherapy. Following a 1:2 propensity score matching based on age, the refined analysis compared 72 patients in the venetoclax-hypomethylating agent group against 112 patients in the intensive chemotherapy group.
The findings demonstrated a clear clinical advantage for the lower-intensity combination during induction. Following one to two cycles, the venetoclax-hypomethylating agent regimen achieved an overall response rate of 80.6% and a complete remission rate of 76.4%. In contrast, the intensive chemotherapy group recorded an overall response rate of 62.5% and a complete remission rate of 50%.
Toxicity, Transfusion Demands, and Survival Benefits
Beyond higher initial response rates, patients receiving the venetoclax-hypomethylating combination experienced reduced hematologic toxicity and lower transfusion requirements. The incidence of febrile neutropenia dropped to 36.1% in the venetoclax group, compared with 56.3% in the intensive chemotherapy arm. Platelet transfusion rates followed a similar trajectory, falling to 50.0% versus 72.3%.
Subgroup analyses further revealed that patients aged 60 years or older, as well as those harboring specific genetic mutations such as FLT3-ITD, DNMT3A, or TET2, exhibited superior responses to the venetoclax-based combination.
Historical Cohort Comparisons and Expert Tension
The evolving preference for less-intensive therapies contrasts with earlier multi-site retrospective data. A separate study published in the journal Blood examined 1,292 patients treated between 2008 and 2012 alongside 695 prospective patients treated between 2013 and 2017, as highlighted by Cleveland Clinic researchers.
In that historical retrospective review, intensive chemotherapy demonstrated superior overall survival compared to less-intensive therapies across all patients. However, subsequent prospective data showed that once models adjusted for age, chance of cure, and performance status, mortality risks between the two treatment approaches narrowed significantly.
“Although the field is moving in the direction of not as readily offering intensive therapies to older patients, there’s still value in it.”
Aaron T. Gerds, MD, MS, Cleveland Clinic Cancer Center
Patient Eligibility and What to Watch Next
Clinical decision-making remains complex. Professional societies continue refining criteria to determine which individuals qualify for intensive induction. Current guidelines incorporate performance status scores, severe cardiac or pulmonary conditions, liver impairment, and reduced creatinine clearance.
As medical centers weigh real-world survival gains against legacy treatment standards, the hematology community awaits further data to settle the debate over optimal induction therapy.
