Redefining antifungal prophylaxis in acute leukaemia in the era of targeted therapies

The therapeutic landscape of acute leukaemia (AL) has evolved profoundly with the introduction of targeted and differentiation agents, altering the epidemiology of invasive fungal disease (IFD). While antifungal prophylaxis with triazoles remains standard for patients receiving intensive chemotherapy, this paradigm may no longer apply to those treated with novel regimens. Targeted agents such as tyrosine kinase inhibitors, blinatumomab, inotuzumab ozogamycin, ivosidenib, gilteritinib, and venetoclax are associated with higher remission rates, shorter or absent neutropenia, and minimal mucosal injury-key determinants of IFD risk. As a result, the incidence of IFD appears markedly lower in such populations. Redefining antifungal prophylactic strategies must account for this therapeutic heterogeneity to avoid overexposure to antifungal drugs and misdirected research priorities. Updated, risk-adapted strategies-integrating treatment intensity, myelotoxicity, and drug interactions-are essential to define which AL patients truly benefit from primary antifungal prophylaxis in the modern era.