Comparative efficacy of antifungal prophylaxis in acute myeloid leukemia: A systematic review and meta-analysis.

e18515 Background: Acute myeloid leukemia (AML) is characterized by prolonged neutropenia and a high risk of infections, including invasive fungal infections (IFI), which are associated with substantial mortality rates of 40–70%. To mitigate this risk, antifungal prophylaxis (AFP) is often used. Current guidelines recommend posaconazole (PCZ) as the agent with the most robust data (Pagano et al. Leukemia 2025), but factors including cost, toxicities, and drug-drug interactions (DDIs) complicate use of common AFP agents, with a dearth of literature directly comparing them. Methods: We conducted a systematic review comparing IFI rate and AFP use in adult and pediatric patients with AML. In total, 2,994 records were identified, of which 367 underwent full-text review. Ultimately, 138 studies were analyzed. 81 studies reported rates of possible, probable, and proven (PsPbPv) IFI while 132 studies reported rates of probable and proven (PbPv) IFI. Patients received intensive therapy (n=78, 57%), less-intensive therapy (n=15, 11%), or both (n=25, 18%). Some (n=20, 14%) studies did not record therapy intensity. A mixed-effects model with PCZ IFI rate as reference/intercept was used. Results: When evaluating the rate of PsPbPv IFI (k=135), first-generation azoles (21.0%, p=0.027) and no AFP (29.2%, p<0.0001) were significantly higher than PCZ (15.3%). Limiting to PbPv IFI rate (k=226), first-generation azoles (9.6%, p<0.0001), amphotericin B (13.2%, p=0.0009), isavuconazole (8.8%, p=0.033), and no AFP (10.7%, p<0.0001) were significantly higher than PCZ (5.0%). IFI rate with voriconazole and echinocandin prophylaxis was not significantly different than PCZ. Subgroup meta-analysis of less-intensive patients was underpowered to detect any difference aside from a higher rate of PsPbPv IFI for first-generation azoles (20.8%, p=0.030) compared to PCZ (9.4%). Conclusions: Our study is the first comparative systematic review of all primary AFP strategies in patients with AML, with considerable dataset of 25,431 patients across 138 studies, the majority with data for patients on intensive therapy (74.6%). Results suggest that echinocandins and second-generation azoles offer comparable protection against PsPbPv IFI. Given the factors complicating the use of these agents including toxicities, DDIs, and no oral formulations, further prospective studies are imperative for further comparison. PsPbPv IFI 95% CI p-value PbPv IFI 95% CI p-value Posaconazole 15.3% 12.6-18.5% --ref-- 5.0% 4.2-6.0% --ref-- Voriconazole 14.3% 10.4-19.3% 0.703 5.7% 4.2-7.5% 0.489 Isavuconazole 15.1% 8.0-26.8% 0.966 8.8% 5.4-13.9% 0.033 First-gen azoles 21.0% 17.1-25.6% 0.027 9.6% 8.0-11.5% <0.0001 Echinocandins 14.0% 8.4-22.5% 0.734 7.0% 4.6-10.5% 0.161 Amphotericin B 28.9% 15.2-47.9% 0.062 13.2% 7.7-21.5% 0.0009 No AFP 29.2% 23.0-36.4% <0.0001 10.7% 8.5%-13.4% <0.0001