Is Antifungal Prophylaxis Needed for Acute Myeloid Leukaemia Patients Treated With Venetoclax-Based Regimens? A Systematic Review and Meta-Analysis.

Acute myeloid leukaemia (AML) patients undergoing venetoclax (VEN)-based regimens are at risk for invasive fungal infections (IFIs), but the benefit of antifungal prophylaxis (AFP) in this setting remains uncertain. We evaluated the efficacy of AFP in preventing invasive fungal infections (IFI), improving overall survival (OS) and best response among AML patients treated with VEN-based therapies. A systematic search of PubMed, EMBASE and Cochrane databases was conducted for studies comparing AFP use to no prophylaxis in AML patients under VEN-based regimens. Data were synthesised using Bayesian meta-analysis. Seven retrospective studies involving 960 patients were included. The pooled analysis yielded an odds ratio (OR) of 0.84 (95% credible interval: 0.39-1.59) for probable or confirmed IFIs with AFP use. The computed probability of OR < 1 for IFI infection was 74.8% for probable or confirmed IFIs and 71.8% for confirmed IFIs, indicating substantial uncertainty and no clear evidence of a real effect. AFP did not significantly alter OS (hazard ratio = 0.82, 95% confidence interval: 0.58-1.16) or response rates. Mould-active antifungals were underutilised in most studies, and the most used antifungals were fluconazole (35.2%) and posaconazole (34.8%). Our analysis highlights the need for prospective studies and risk stratification to evaluate the role of mould-active agents in this population.