LAUSR

Abstract Background Isavuconazole (ISA) is a novel triazole antifungal approved for treating invasive aspergillosis and mucormycosis. While ISA is increasingly used for prophylaxis in hematologic malignancy patients when other azoles are contraindicated, there are currently limited data on breakthrough invasive fungal infection (IFI) rates in this context. Methods We retrospectively reviewed inpatient and outpatient pharmacy records from March 2015 to April 2018 to identify adult patients with hematologic malignancy who received at least 7 days of ISA for prophylaxis. Breakthrough IFI was defined by EORTC-MSG criteria. Results We identified 73 hematologic malignancy patients who received ISA; 29 received at least 7 days ISA for prophylaxis in 33 separate episodes. Of these patients, 52% had acute myeloid leukemia, 14% had acute promyelocytic leukemia, 10% had myelodysplastic syndrome, and 21% had another malignancy. Eighty-six percent of patients were neutropenic (median duration 24 days; range 2–213). Median duration of ISA prophylaxis was 61 days (range 8–635). The most common reason for choosing ISA over other antifungal agents was QTc prolongation (45%), followed by intolerance of other antifungals (27%) and drug-drug interactions with other azoles (21%). Four patients (12%) developed proven or probable breakthrough IFI (Table 1). Among patients with breakthrough IFI, mortality was 50% at 12 weeks. Table 1. Characteristics of Breakthrough IFI Among Hematologic Malignancy Patients Receiving ISA Prophylaxis Age/Gender Disease IFI site Organism Diagnostic Test ANCNadir Neutropenia Duration (days) Duration ISA (days) Outcome (12 weeks) 32M AML Lung Aspergillus fumigatus BAL: fungal culture <10 118 38 Death 65M Aplastic anemia Blood, lung Scedosporium apiospermum Blood culture <100 14 13 Death 44F ALL Lung Aspergillus nigri Lung FNA: PCR, path 0 143 52 Partial response 63F AML Lung Unknown* Lung FNA negative 110 90 73 Partial response *Probable IFI; other threecases were proven. Conclusion We demonstrate a 12% rate of breakthrough IFI among hematologic malignancy patients on ISA prophylaxis, similar to published rates (10–15%) on posaconazole prophylaxis. Further study is needed to characterize risk factors for and epidemiology of ISA breakthrough. Disclosures S. B. Doernberg, Genentech: Consultant, Consulting fee. Actelion: Consultant, Consulting fee.