Antimicrob Agents Chemother. 2026 Mar 31:e0110125. doi: 10.1128/aac.01101-25. Online ahead of print.
ABSTRACT
Venetoclax (VEN), a selective BCL-2 inhibitor predominantly metabolized by CYP3A4, is a cornerstone therapeutic for myeloid neoplasms (MNs). Patients with myeloid malignancies are at elevated risk of invasive fungal infections (IFIs), and triazole antifungal drugs, such as posaconazole (PCZ) and voriconazole (VCZ), are commonly used for prophylaxis or treatment. These agents are potent CYP3A4 inhibitors and will exhibit significant potential for pharmacokinetic drug-drug interactions with VEN. Although studies on their interaction are limited, such combinations are frequently used in clinical practice, making further research highly significant. This study aimed to investigate the changes in blood concentration and the safety of VEN when combined with triazole antifungal drugs (PCZ and VCZ). Patients with MN treated with VEN from April 2023 to April 2025 were enrolled and allocated to the VEN monotherapy group and the VEN plus triazole antifungal drug group. We collected baseline demographic characteristics and monitored adverse events. Steady-state plasma concentrations of VEN were quantified using the liquid chromatography-mass spectrometry methodology. Statistical analyses, including comparative assessments of plasma concentrations and adverse event rates, were performed using IBM SPSS Statistics 26. A total of 54 patients were enrolled in the study. Following VEN dose reduction to 100 mg, plasma concentrations in the VEN + PCZ/VCZ group remained significantly elevated compared to the VEN group (P < 0.001). However, the magnitude of this elevation did not differ significantly between the VEN + PCZ group and the VEN + VCZ group (P = 0.176). In addition, there was no linear correlation between VEN concentration and PCZ/VCZ concentration. Safety analysis revealed no statistically significant differences between the two groups in the incidence of grade ≥3 hematological adverse events (P = 0.214) or severe (grade ≥3) gastrointestinal adverse events (P = 0.671). VEN combined with PCZ or VCZ resulted in significantly higher VEN exposure without a corresponding increase in severe hematological or gastrointestinal toxicity. This strategy effectively mitigates IFI risk without compromising the safety profile of VEN therapy.
PMID:41915767 | DOI:10.1128/aac.01101-25
