Risk Factors for Infectious Adverse Events in Newly Diagnosed Acute Myeloid Leukemia Patients Treated With Venetoclax Combinations: A Retrospective Single-Centre Real-World Experience.

[BACKGROUND] Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern.

[AIMS] This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting.

[METHODS AND RESULTS] We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥ 2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5-35). A total of 34 (23.8%) grade ≥ 2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR = 1.037, p = 0.005) and interacting concomitant medications (OR = 9.99, p < 0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs.

[CONCLUSION] IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.