Real-World Experience of Voriconazole Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients: A Single-Center Study

BACKGROUND: High rates of discontinuation of voriconazole (VCZ) antifungal prophylaxis (AFP) due to toxicities have been reported from single centers in allogeneic hematopoietic (allo-HCT) recipients. We sought to describe (i) adherence to AFP guidelines and (ii) reasons for premature VCZ discontinuation (D/C). METHODS: Retrospective review of 215 adult allo-HCT recipients from September 1, 2014–December 31, 2015 at our center. Per standards of care (SOC), patients received micafungin from Day 2 post-allo-HCT, then switched to VCZ by D7 unless contraindicated, and remained on AFP until cessation of immunosuppression or D100 for high-risk patients. AFP modification, D/C and treatment emergent adverse events (TEAE) regardless of causality were captured through D100. Standard definitions were used for invasive fungal infections (IFI). RESULTS: Of 215 patients, 42 had contraindications to VCZ at baseline. Of 173 patients included in the analysis, 65 (37.6%) received ex vivo T-cell depleted (TCD) peripheral blood (PB), 15% cord and 47.4% conventional PB or marrow allografts. All TCD recipients received myeloablative conditioning (MA) and all cord recipients received reduced intensity conditioning (RIC). For conventional transplant, 65.9 and 26.8% of the patients received RIC and MA, respectively. One hundred and sixty-eight (97%) patients had normal liver function tests (LFT) at VCZ initiation. One hundred and twenty-nine (74.6%) patients started VCZ by D7 and 95% started by D15. Median duration of VCZ AFP was 68D (IQR 22–91). Abnormal LFTs was the most frequently encountered TEAE (42/58, 72%), followed by neurologic/visual TEAE (11/58, 19%) leading to VCZ D/C. Median time to VCZ D/C due to neurologic/visual TEAE (4D, IQR 4–9) was significantly shorter than abnormal LFTs (25D, IQR 16–42) (P < 0.05). Eight (5%) breakthrough proven/probable IFIs were observed by D180, without significant difference based on transplant types or AFP duration. Duration and reasons for VCZ D/C were shown in Table 1 by HCT type. CONCLUSION: 75% of the patients started VCZ per SOC and 95% by D15. Most TEAE leading to VCZ D/C were abnormal LFTs in all HCT types, and most commonly in cord HCT. 3) Neurologic/visual TEAE were similar across types. Rates of IFI were 3–4% in CONV and TCD and 12% in UCB. DISCLOSURES: Y. T. Huang, Merck & Co.: Grant Investigator, Research grant. M. A. Perales, Merck: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. Astella: Consultant, Grant Investigator and Investigator, Consulting fee and Research grant. G. Papanicolaou, Astellas Pharma: Consultant and Grant Investigator, Consulting fee, Research grant and Research support. Merck &Co: DSC member and Investigator, Consulting fee, Research grant and Research support