Caspofungin for Primary Antifungal Prophylaxis in Acute Myeloid Leukemia: A Real-Life Study from an Academic Center

<b>Background:</b> Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. <b>Study Objective:</b> This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. <b>Methods:</b> A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021-2025). Patients received either caspofungin or posaconazole as PAP based on the drug-drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). <b>Results:</b> IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; <i>p</i> = 0.878). Post-chemotherapy refractory AML (OR = 11.9; <i>p</i> = 0.003) and liver disease (OR = 30.4; <i>p</i> = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, <i>p</i> = 0.6). <b>Conclusions:</b> Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies.