Treatment of Acute Myeloid Leukemia patients over the age of 80 with venetoclax and azacitidine

Abstract Introduction: Octogenarians and Nonagenarians diagnosed with acute myeloid leukemia (AML) are frequently excluded from clinical trials and, until recently, were most commonly referred to supportive care only. The establishment of venetoclax (ven) and azacitidine (aza) as the current standard of care for AML patients unfit for intensive chemotherapy has led to increased selection of AML patients over the age of 80 for anti-leukemic treatment. We describe our experience treating this elderly patient population with ven-aza. Methods: We retrospectively analyzed the patient records of all patients with AML diagnosed at our center between January 2019 and May 2025 who received first line treatment with ven-aza. We compared patient and disease characteristics, as well as treatment characteristic and outcomes between patients over and under the age of 80. This study was approved by our local institutional review board. Results: We included 160 patients with newly diagnosed AML patients who were treated with ven-aza as first line treatment (median age 77), 60 of which were over the age of 80(>80). The median age of the >80 group was 84 years (range 80-95) vs 73 years (range 40-79) for the under 80 (<80) group (p<0.001). Of the entire cohort, 57% were male, 18% had an ECOG performance status of 3-4, 44.7% had adverse ELN 2022 risk AML and 49% had secondary AML. Theses patient and disease characteristics were not significantly different between the >80 and <80 groups. Additional characteristics such as cell counts, bone marrow blast counts, and LDH and creatinine levels at the time of diagnosis were similar between the two groups. The median time from diagnosis to treatment was 6 days (IQR 3-10 days) and was similar between patients >80 and <80. In the entire cohort, 67.7% of patients achieved complete remission (CR)/ CR with incomplete count recovery (CRi). In the >80 group 66.1% achieved CR/CRi vs. 68% in the <80 group (p=0.862). 30 day mortality was 10% in the >80 group vs. 9.1% in the <80 group (p=0.849). Overall, 18.8% of patients underwent an allogeneic stem cell transplant (SCT) in CR1. No patients >80 underwent SCT and 30% of patients <80 underwent SCT during first line treatment. Median follow up was 21.8 months. Overall survival (OS) was significantly lower in patients >80 than in patients <80 (median OS 6.5 months vs. 13 months, p=0.006). 18 month OS was 27.4% vs 44.3%, respectively. When censoring for SCT, no statistical difference was observed between patients >80 and <80 (median OS 6.53 months vs. 9.67 months respectively, p=0.251). Multivariate analysis for OS including age>80, ECOG 3-4, ELN unfavorable risk, Secondary AML, and SCT identified age>80 as an independent risk factor (HR 1.63 95% CI 1.08-2.46 p=0.019) as well as ECOG 3-4 (HR 2.11, 95% CI 1.33-3.36, p=0.002) and secondary AML (HR 1.8 95% CI 1.19-2.71, p=0.005). ELN risk was not independently associated with OS, whereas SCT showed a trend for improved OS (HR 0.61, 95% CI 0.34-1.08, p=0.087). Median relapse free survival (RFS) was 26.4 months for the entire cohort and was not significantly different in univariate analysis between patients >80 and <80 although a trend is apparent for improved RFS in the <80 group (median RFS 17 vs. 32 months, p=0.063). Censoring forSCT abolished this trend. Multivariate analysis including age > 80, secondary AML, adverse ELN risk and SCT found age > 80 to be significantly associated with poor RFS ( HR 2.19 95% CI 1.11-3.33 p =0.025) as well as secondary AML (HR 2 95% CI 1.05-3.79 p=0.033). Conclusions:AML patients over the age of 80 who receive ven-aza achieve high rates of CR/CRi, similarly to younger patients, and can achieve prolonged remission free and overall survival outcomes. Whereas lower survival outcomes are observed for patients >80, this seems largely driven by the 30% of patients younger than 80 years old who underwent allogeneic stem cell transplant.