Infections of Venetoclax-Based Chemotherapy in Acute Myeloid Leukemia: Rationale for Proper Antimicrobial Prophylaxis

Although venetoclax (VEN)-based combination chemotherapy in patients with acute myeloid leukemia (AML) results in prolonged and profound neutropenia, data regarding infectious complications and antimicrobial prophylaxis are lacking. We investigated the infectious complications in 122 adult patients with AML under the same standard of care for prevention. The prophylaxis protocol was fluconazole 400 mg/d without antibacterial agents. The incidence of proven or probable invasive fungal infections (IFIs) was 6.6/100 cycles, and 22 patients (18.0%) were diagnosed (median, second cycle; interquartile range, 1-2). All IFIs were caused by Aspergillus and significantly influenced the overall mortality (odds ratio (OR), 2.737; 95% confidence interval (CI), 1.051-7.128; p = 0.034). In the multivariate analysis, secondary or therapy-related AML was an independent risk factor for IFIs (OR, 3.859; 95% CI, 1.344-11.048, p = 0.012). A total of 39 bloodstream infection (BSIs) episodes occurred in 35 patients (28.7%), with an incidence of 12.7/100 cycles. High-dose steroid administration within 90 days was associated with the occurrence of BSIs (OR, 7.474; 95% CI; 1.661-3.631, p = 0.008), although BSIs themselves did not have an impact on the outcomes. Our findings suggest evidence for the need for mold-active antifungal agents as antifungal prophylaxis, rather than fluconazole, especially in patients with secondary or therapy-related AML.