To better characterize the infection risk profile associated with venetoclax-based regimens in AML, we conducted a retrospective analysis of newly diagnosed, untreated non-M3 AML patients at our center from 2015 to 2024. Patients with active infections, prior treatment, or incomplete data were excluded; eligible patients were divided into VEN-based or conventional chemotherapy groups. After 1:1 propensity score matching (n = 115 per group), baseline characteristics—including age, sex, BMI, bone marrow blast percentage, prognostic category, AML type, hematopoietic cell transplantation-comorbidity index (HCT-CI), and absolute neutrophil count (ANC)—were balanced (standardized mean difference [SMD] < 0.2). Infection events were monitored from the initiation of chemotherapy until the earliest of 180 days, hematopoietic stem cell transplantation, last follow-up, or death (“risk days”), by BMT CTN MOP v3.0. Using standardized criteria, Infections were classified as any microbiologically documented infection (subdivided into bacterial, fungal, or viral). Events with a clinically significant pathogen were classified as “microbiologically documented”; those without pathogen identification, including possible invasive fungal infections, were classified as “clinically documented.” Infection density was calculated per 1,000 person-days using Poisson regression, and cumulative incidence at each time point was compared between groups by Kaplan-Meier and log-rank tests.

In the VEN-based group, 50 patients (43.48%, 97 events) had granulocytopenia-related infections vs. 62 (53.91%, 95 events) in controls; infection densities were 14.73 vs. 13.11 per 1,000 person-days. Upper respiratory and pulmonary infections were both less frequent in the VEN-based group (3.48% vs. 15.65%, density 0.61 vs. 2.35; OR = 0.21, P = 0.006; IRR = 0.45, P = 0.0148; pulmonary: 53.91% vs. 69.57%, density 11.24 vs. 17.11; OR = 0.51, P = 0.021), though the density difference for pulmonary infections was not significant (IRR = 1.14, P = 0.386). No significant group differences were seen for sepsis, gastrointestinal, oral, or urinary infections. Skin/soft tissue and perianal infection densities were higher in the VEN-based group (1.37 vs. 0.83; IRR = 2.86, P = 0.047 and 0.91 vs. 0.28; IRR = 5.71, P = 0.033), but overall incidence was similar. Bacterial and fungal infections were lower in the VEN-based group (bacterial: 24.35% vs. 39.13%, density 4.56 vs. 6.35; OR = 0.67, P = 0.016; fungal: 24.35% vs. 44.35%, density 4.25 vs. 6.90; OR = 0.19, P = 0.001), while viral infections were slightly higher (21.74% vs. 20.00%, density 4.71 vs. 3.59; P > 0.1).

The cumulative incidence of first infection was consistently lower in the VEN-based group at 30, 60, and 90 days (0.45, 0.60, 0.68) compared to the non-VEN group (0.57, 0.74, 0.79; all p < 0.05), but with no significant difference (p = 0.2). For microbiologically confirmed infections, the cumulative incidence in the VEN-based group is slightly higher than in the non-VEN group, but no statistical significance (p > 0.2). Subtype analysis showed that bacterial and fungal infection incidence was lower in the VEN-based group at all time points, though not statistically significant. Conversely, viral infection incidence was significantly higher in the VEN-based group (0.15–0.26 vs. 0.03–0.08; all p < 0.01).

Kaplan-Meier analysis showed that, within 90 days, microbiologically confirmed, bacterial, or fungal infections were associated with significantly reduced PFS at 100 days (p = 0.039, 0.023, and 0.046, respectively), whereas viral infections had no effect. At 365 days, the reduction in PFS persisted for microbiologically confirmed (p = 0.027) and bacterial infections (p = 0.04), and was marginally significant for fungal infections (p = 0.075).

In this real-world retrospective study, venetoclax-based therapy in newly diagnosed AML patients was linked to a lower overall infection burden—especially fewer respiratory, bacterial, and fungal infections—than conventional regimens, but with higher skin and perianal infection densities. Early microbiologically confirmed infections within 90 days were associated with worse progression-free survival, highlighting the importance of early, targeted infection management in high-risk patients.

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2025
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