How to safely discontinue antifungal treatment in invasive pulmonary aspergillosis?-clinical considerations in haematology

Abstract

Background: Treatment duration in invasive pulmonary aspergillosis (IPA) in patients with haematological malignancies is not well defined through clinical trials and is therefore often driven more by experience than evidence, with implications for outcome, patient quality-of-life, drug toxicity, costs, and antifungal stewardship.

Objectives: To review current evidence and provide expert considerations regarding cessation of antifungal therapy for IPA, and to propose pragmatic criteria and follow-up strategies to guide safe discontinuation and early detection of recurrence.

Sources: Narrative review of clinical trials, observational and biomarker studies, imaging data, and expert guidance related to IPA treatment response, recurrence, and antifungal toxicity.

Content: Shared definitions of treatment success exist, but standardized criteria for treatment failure, stable disease, and stopping therapy are lacking. Decisions to discontinue antifungals rely on individualized assessment of host immune status and recovery, clinical stability, mycological markers (notably serum galactomannan), and imaging findings, primarily chest computed tomography, with adjunctive roles for [¹⁸F] Fluorodeoxyglucose Positron Emission Tomography and emerging biomarkers. All of the above have limited sensitivity, require thorough interpretation, and are to be used as a bundle, not as standalone criterion. Our review outlines prerequisites for stopping treatment, structured surveillance after cessation, triggers for immediate re-evaluation, and scenarios in which treatment should not be stopped. Risks of recurrence, particularly in persistently immunocompromised patients, are weighed against cumulative toxicity and drug-drug interactions of prolonged antifungal use. Management options for antifungal toxicity and potential utility of novel antifungal agents are discussed.

Implications: Stopping antifungal therapy for IPA should be a standardized and patient-specific decision supported by predefined monitoring and rapid response pathways within standardized institutional procedures. Prospective trials comparing cessation strategies are needed to increase knowledge on optimal duration, in specific during reoccurring or ongoing immunosuppression.

Keywords: Antifungal stewardship; Invasive mycoses; Randomized clinical trial; Treatment duration.