Primary Amphotericin B Monotherapy Versus Combination with Azoles or Echinocandins for Invasive Aspergillosis in Hematologic Malignancies: Comparable Outcomes over 22 Years in a Large Single-Center Cohort

Introduction: Invasive aspergillosis (IA) remains a major cause of mortality in patients with hematologic malignancies. Although combination antifungal therapy with lipid formulations of amphotericin B (AmB) plus an azole or echinocandin is widely used, its survival benefit over monotherapy remains uncertain. Methods: We identified 912 patients with proven or probable IA diagnosed between January 2003 and October 2025, of whom 831 (91%) received ≥5 days of primary antifungal therapy. Among these, 305 patients who received an amphotericin B (AmB)-containing regimen were included in the study, including AmB monotherapy (n = 69), AmB plus an azole (n = 200), and AmB plus an echinocandin (n = 36). Inverse probability of treatment weighting (IPTW)-adjusted competing risks regression was used to assess the association between primary therapy (AmB monotherapy vs. combination therapy with an azole or echinocandin) and 6- and 12-week IA-related mortality. Results: Multivariable competing risks analyses identified age ≥65 years, persistent neutropenia, and ICU admission as independent predictors of IA-related mortality. IPTW-adjusted analyses confirmed no significant association between treatment regimen and IA-related mortality. Conclusions: Primary combination therapy was not associated with lower IA-related mortality than AmB monotherapy. Outcomes were driven primarily by disease severity markers, including older age, persistent neutropenia, and ICU admission.