Antifungal Prophylaxis in the Era of Targeted Chemotherapy for Acute Myelogenous Leukemia

Abstract

Purpose of Review: This review will provide an overview of the potential drug-drug interactions (DDIs) that may occur when using small-molecule kinase inhibitors (SMKIs) for the treatment of acute myeloid leukemia (AML) with triazole antifungals. We aim to discuss the management strategies for these interactions, including the assessment of invasive fungal disease (IFD) risks, alternative antifungal treatments, and dosage adjustments of SMKI therapy. Recent Findings: Recent advances in molecular and cell biology have led to the approval of several SMKIs for the treatment of AML. These targeted therapies, while more tolerable than traditional cytotoxic chemotherapy regimens, are metabolized via the cytochrome P450 3A4 pathway, making them susceptible to potential DDIs with triazole antifungals. Managing these interactions requires a tailored approach, taking into consideration the patient’s specific IFD risks, treatment status, and comorbidities. While specific dosing guidance is available for using venetoclax or ivosidenib with triazole antifungals, recommendations for other SMKIs are less certain. Summary: The use of SMKIs in AML treatment has revolutionized patient care by providing more targeted and tolerable therapies. However, the potential for DDIs, particularly with triazole antifungals, necessitates careful management. Clinicians must carefully assess the specific IFD risks associated with SMKI therapies, evaluate the limitations of current and future antifungal treatments, and consider evidence supporting dosage adjustments when co-administering SMKIs with triazoles. Ongoing research in model-informed precision dosing and therapeutic drug monitoring holds promise for improving the safety and efficacy of managing drug interactions with SMKI therapy.