P083 | DOSE-ADJUSTED VENETOCLAX WITH ANTIFUNGAL PROPHYLAXIS PRESERVES EFFICACY AND LIMITS FUNGAL INFECTIONS IN ELDERLY ACUTE MYELOID LEUKEMIA: A SINGLE-CENTER EXPERIENCE

Background: Acute myeloid leukemia (AML) in elderly patients with comorbidities is associated with poor outcomes. The combination of azacitidine (AZA) and the BCL-2 inhibitor venetoclax (VEN) has significantly improved clinical outcomes in this population compared to AZA alone. This regimen induces profound neutropenia increasing the risk of invasive fungal infections (IFI). Azole-based antifungal prophylaxis is commonly used but can interfere with VEN metabolism, requiring dose adjustments and raising concerns about reduced treatment efficacy. We aimed to assess the incidence of IFIs and hematologic response in AML patients receiving AZA/VEN with concurrent antifungal prophylaxis. Methods: This retrospective observational study included 26 AML patients treated with AZA/VEN (median age, 74 years old; range, 68-80; M/F, 18/8) at the Hematology and Transplant Center, University Hospital “San Giovanni di Dio e Ruggi d’Aragona”, Salerno, Italy, between March 2022 to April 2025. Patients with prior history of IFI were excluded. The primary endpoint was the incidence of IFIs during AZA/VEN therapy with antifungal prophylaxis. The secondary endpoint was overall response rate (ORR). IFI diagnosis was based on clinical assessment, CT imaging, bronchoscopy, galactomannan antigen, and/or Aspergillus DNA testing. Results: According to ELN-2022, 84.6% of patients had intermediate or adverse-risk AML. Antifungal prophylaxis was administered in 96.1% of cases (posaconazole: 76.9%, isavuconazole: 15.4%, caspofungin: 3.8%). VEN dosing was reduced in all prophylaxed patients: to 70 mg in 38.5% and to 100 mg in 57.7%. The ORR was 88.5%, including 14 complete remissions (CR) and 9 complete remissions with incomplete count recovery (CRi). Fever occurred in 57.6% of patients but only 2 cases met criteria for possible IFI. Median overall survival was 14.4 months; median progression-free survival was 13.9 months. Only one patient died due to septic shock. Conclusions: Our real-world experience confirms the high efficacy of AZA/VEN, even with dose-reduced VEN and concomitant antifungal prophylaxis. Importantly, the incidence of IFIs remained low, and no increase in severe neutropenic complications was observed. These findings support the safety and feasibility of antifungal prophylaxis alongside VEN-based regimens in elderly AML patients, reinforcing their integration into routine clinical practice.