Objective  To evaluate the therapeutic efficacy, safety, and factors influencing overall survival (OS) in patients with newly diagnosed acute myeloid leukemia (unfit AML) treated with venetoclax (VEN) plus low-dose cytarabine (LDAC) treatment regimen.

Methods  In this study, we retrospectively analyzed clinical data from 33 patients with unfit AML treated with VEN plus LDAC at the Affiliated Hospital of Jiangsu University between December 2019 and January 2024. The efficacy and survival outcomes of this regimen were assessed.

Results Thirty-three patients (median age: 72 years) were enrolled, including 29 with de novo AML and four with secondary AML. The median follow-up duration was 781 days, with a median OS and progression-free survival (PFS) of 467 days (range: 104–812 days) and 395 days (range: 104–637 days), respectively. After induction chemotherapy, the overall response rate (ORR) was 69.7%, with a composite rate of complete response (CR) and CR with incomplete blood count recovery (CRi) reaching 36.4%. Morphologic leukemia-free state (MLFS) and partial remission (PR) were observed in 3% and 30.3% of patients, respectively. The median number of treatment cycles was three (range: 1–6.5). Treatment-related adverse events were primarily hematological, with high rates of grade 3–4 hematologic toxicities. Kaplan–Meier analysis revealed significant associations between survival and ECOG performance status, TP53 mutation status, treatment cycles, and response (P<0.05). Univariate and multivariate Cox regression analyses identified treatment cycles as an independent risk factor for OS (P<0.05).

Conclusions The VEN plus LDAC regimen demonstrated feasibility and efficacy in patients with newly diagnosed AML; initial response and continuous treatment were associated with favorable survival.