(212) Safety and Efficacy of Voriconazole versus Posaconazole Antifungal Prophylaxis in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Poster Abstract: Background/Rationale: Invasive fungal infections (IFIs) afflict up to 40% of patients with hematologic malignancies.1 Current national guidelines recommend that patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) receive primary antifungal prophylaxis through periods of neutropenia with preference given to posaconazole over alternative antifungal agents, including voriconazole.2 Notably, posaconazole provides protection against Mucorales while voriconazole does not.3 Limited retrospective literature has attempted to compare the efficacy of posaconazole over voriconazole with respect to the incidence of breakthrough invasive fungal infections (bIFIs), and data are mixed.4,5 Institutional guidelines for the prevention of IFIs in patients with AML or MDS were updated in 2021 to denote posaconazole as the preferred agent for primary antifungal prophylaxis. Prior to this change, voriconazole was frequently prescribed for primary antifungal prophylaxis. Considering the higher cost of posaconazole and the rarity of mucormycosis, the theoretical benefit gained by escalating primary antifungal prophylaxis from voriconazole to posaconazole remains ambiguous.

Objectives: The primary objective of this study is to compare the incidence of bIFIs among patients with AML or MDS who received primary antifungal prophylaxis per institutional guidelines with either voriconazole or posaconazole. Secondary objectives include comparisons of IFI incidence, amphotericin B utilization, drug discontinuation due to proven or suspected toxicity, percentage of antifungal agent trough levels within goal, and survival among those who received voriconazole versus posaconazole prophylaxis.

Methods: This retrospective cohort study will include ~200 adult patients with either AML or MDS who received voriconazole or posaconazole prophylaxis between April 1st, 2019 and April 1st, 2023. Patients who underwent stem cell transplant or who received immunosuppression against graft-versus-host disease within one year prior to the initiation of antifungal prophylaxis will be excluded.

Results: At the time of submission, data collection and analysis are ongoing. Final Results will be presented at the HOPA Annual Conference 2024.

Discussion/

Conclusion: Conclusions are pending final results and will be presented at the HOPA Annual Conference 2024. The results of this project will allow us either to affirm the clinical validity of current institutional antifungal prophylaxis guidelines or to suggest revisions to ensure that optimal patient care standards are in place.

References (must also be included in final poster): 1. Tacke D, Buchheidt D, Karthaus M, et al. Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology. Annals of Hematology. 2014;93:1449-1456.
2. Baden LR, Swaminathan S, Almyroundis NG et al. Prevention and treatment of cancer-related infections. NCCN Clinical Practice Guidelines in Oncology. Version 1.2023.
3. Jenks JD, Cornely OA, Chen SCA, et al. Breakthrough invasive fungal infections: Who is at risk? Mycoses. 2020;63:1021-1032.
4. Ananda-Rajah MR, Grigg A, Downey MT, et al. Comparative clinical effectiveness of prophylactic voriconaole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period. Infectious Complications in Hematology. 2012;97(3):459-463.
5. Hachem R, Assaf A, Numan Y, et al. Comparing the safety and efficacy of voriconazole versus posaconazole in the prevention of invasive fungal infections in high-risk patients with hematological malignancies. International J of Antimicrobial Agents. 2017;50:384-388.