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May 30, 2026

Real-world comparative effectiveness of decitabine/cedazuridine plus venetoclax versus azacitidine plus venetoclax in older or unfit patients with newly diagnosed acute myeloid leukemia.

Key Points

Evaluate the survival and adverse event outcomes of decitabine/cedazuridine plus venetoclax versus azacitidine plus venetoclax in older or unfit patients with newly diagnosed AML.
Retrospective cohort study using TriNetX electronic health records.
Included older patients (>50 years) receiving first-line treatment with either decitabine/cedazuridine plus venetoclax or azacitidine plus venetoclax.
Propensity score matching for comorbidities and key demographic factors was performed.
At 1 year, the all-cause mortality for decitabine/cedazuridine (CDV) was 32.6% versus 42.5% for azacitidine (AV), with hazard ratio (HR) 0.739, p=0.047.
CDV showed significantly reduced risk for anemia (HR 0.510, p=0.0001) and neutropenic fever (HR 0.554, p<0.0001) at 1 year compared to AV.
Survival at 2 years was also better for CDV, with a mortality rate of 37.8% versus 49.8% for AV, HR 0.704, p=0.013.

Abstract

e18533 Background: Older and medically unfit patients with Acute Myeloid Leukemia (AML) are unable to tolerate intensive induction chemotherapy and historically experience poor survival. The addition of venetoclax to hypomethylating agents (HMAs) has significantly improved outcomes in this population. However, real-world outcomes frequently differ from clinical trial results due to comorbidity burden, treatment interruptions, and toxicity. Oral decitabine/cedazuridine offers pharmacokinetic equivalence to intravenous decitabine and greater treatment convenience, yet comparative real-world effectiveness and safety data versus venetoclax/azacitidine remain limited. We evaluated survival and adverse event outcomes between these regimens in a multi-center real-world cohort. Methods: CWe performed a retrospective cohort study using the TriNetX federated electronic health record network. Adults >50 years with newly diagnosed AML receiving first-line decitabine/cedazuridine plus venetoclax (CDV) or azacitidine plus venetoclax (AV) were included. Patients with acute promyelocytic leukemia or prior stem cell transplantation were excluded. Propensity score matching was conducted for age, sex, race, prior myelodysplastic syndrome, TP53 status, and Charlson Comorbidity Index–associated conditions. All analysis were carried out post matching. The primary outcome was all-cause mortality (ACM). Secondary outcomes included anemia, neutropenic fever, neutropenia, major adverse cardiovascular and cerebrovascular events (MACCE), tumor lysis syndrome, and sepsis. Outcomes were assessed at 6 months, 1 year, and 2 years using Kaplan–Meier analysis and Cox proportional hazards models. Results: After matching, 233 patients were included per cohort. ACM for CDV versus AV at 6 months, 1 year, and 2 years was 21.0% vs 27.9%, 32.6% vs 42.5%, and 37.8% vs 49.8%, respectively. Compared to AV, CDV significantly reduced the risk of mortality at 1 year (HR 0.739; 95% CI 0.548-0.997, p=0.047) and 2 years (HR 0.704; 95% CI 0.533-0.929, p=0.013). At 1 year, CDV was associated with reduced hazard of anemia (HR 0.510, 95%CI 0.433-0.765, p=0.0001), neutropenic fever (HR 0.554, 95%CI 0.427-0.719, p<0.0001), and MACCE (HR 0.606, 95%CI 0.360-0.961, p=0.045), with no significant differences in neutropenia, tumor lysis syndrome, or sepsis. Conclusions: In this real-world analysis of older or unfit patients with newly diagnosed AML, CDV was associated with significantly improved survival and a favorable toxicity profile compared with AV. These findings extend pivotal trial data into routine clinical practice and suggests CDV may have a clinically meaningful advantage over AV in this high-risk population. Prospective studies are warranted to confirm these observations and refine frontline treatment selection.

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