Antifungal prophylaxis in patients with acute myeloid leukaemia treated with venetoclax and azacitidine

Overview

Invasive fungal diseases (IFDs) represent a serious cause of morbidity and mortality in patients with acute myeloid leukaemia (AML) treated with intensive therapy, particularly following induction chemotherapy and allogeneic haematopoietic stem cell transplantation. The combination of the BCL-2 inhibitor venetoclax with the hypomethylating agent azacitidine (VEN+AZA) has become standard therapy for patients unfit for intensive chemotherapy, leading to a significant improvement in outcomes, especially when followed by allogeneic transplantation. However, this regimen may be associated with prolonged neutropenia and other factors that substantially increase the risk of IFDs. Published retrospective studies report highly variable incidences of IFDs (0.5–26%) and inconsistent effects of antifungal prophylaxis, largely due to marked heterogeneity of the evaluated cohorts, differences in the use and type of antifungal prophylaxis, definitions of IFDs, and other variables. Nevertheless, most studies have not demonstrated a significant impact of prophylaxis on the incidence of IFDs, although their purely retrospective design must be taken into account. In addition, drug–drug interactions between venetoclax and azole antifungals may pose a potential risk by increasing venetoclax toxicity. Based on currently available data, routine antifungal prophylaxis is not universally indicated, but should be considered only in defined high-risk patient groups (relapsed/refractory AML, a history of IFD, or prolonged severe neutropenia). The aim of this article was to summarise the available evidence on the efficacy and safety of antifungal prophylaxis in patients with AML treated with the VEN+AZA regimen. This review highlights the need for prospective studies and risk stratification to allow a more detailed assessment of the role of antifungal prophylaxis in this patient cohort.

Keywords:

acute myeloid leukaemia – venetoclax – azacitidine – antifungal prophylaxis