Presenting Author: Matthew Yacobucci, PharmD, BCOP, Albany College of Pharmacy and Health Sciences, Albany, NY
Co-Authors: Zhenzi Hong, Colby Webster, Alexis Gregoire, and Ejemen Aigbedion, PharmD Candidates, Albany College of Pharmacy and Health Sciences, Albany, NY
BACKGROUND: Patients with acute leukemia have a high risk for invasive fungal disease (IFD). Per the NCCN guidelines, antifungal prophylaxis is recommended for patients with acute leukemia and neutropenia for the prevention of IFD. Triazoles are often employed for antifungal prophylaxis, but patients are prone to drug interactions with oral anticancer agents.
OBJECTIVE: To assess the prescribing patterns, efficacy, and safety of antifungal prophylaxis among patients with acute leukemia who received induction chemotherapy including an oral anticancer agent metabolized through CYP450.
METHODS: This was a single-center, retrospective-cohort analysis conducted from July 2020 to August 2024. The inclusion criteria were age >18 years, a diagnosis of acute leukemia, and receiving oral anticancer therapy with induction treatment. Patients were excluded from the study because of incomplete data. Patients were identified through the electronic health record, and the data that were extracted included demographics, laboratory values, vitals, acute leukemia subtype, new leukemia diagnosis or relapse, induction chemotherapy regimen, antifungal prophylaxis, previous antifungal use, previous fungal infection(s) and treatment, coinfections, response achieved after induction, and adverse events.
RESULTS: A total of 128 patients were included in the study. Most patients had acute myeloid leukemia (94%), with most being new diagnoses (68%). The median age was 69 years, and 59% of the patients were male. The leukemia prognostic risk categories were 55% poor risk, 39% intermediate risk, 4% favorable risk, and 2% unknown risk. Most patients were prescribed antifungal prophylaxis (87%), with 46% receiving micafungin, 7% triazoles, and 34% sequential therapy (micafungin or triazole followed by the other). The oral chemotherapy agents received included venetoclax (78%), midostaurin (14%), dasatinib (4%), ponatinib (2%), and ivosidenib (1%). In all, 3 patients had proven IFD (2 with micafungin and 1 with subsequent therapy) and 11 patients had possible IFD (6 with micafungin, 1 with voriconazole, 3 with subsequent therapy, 1 with no prophylaxis). Adverse events were observed across all of the groups, including micafungin (grade 1 or 2, 14.9%; grade 3 or 4, 11.2%), triazole (grade 1 or 2, 8.6%; grade 3 or 4, 8.9%), subsequent therapy (grade 1 or 2, 15.3%; grade 3 or 4, 14%), and no prophylaxis (grade 1 or 2, 6.4%; grade 3 or 4, 6.8%).
CONCLUSION: The prescribing patterns favored micafungin for antifungal prophylaxis. Patients who received micafungin alone had an increased incidence of IFD. The micafungin and subsequent therapy groups had the highest rates of adverse events. Because of the small sample size and low rates of IFD, a larger study is needed to evaluate the preferred antifungal prophylactic agent for patients with acute hematologic malignancies receiving induction therapy with oral anticancer agents that interact with azole antifungals.
- Department of Health and Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0. November 27, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf
- Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2020;71:1367-1376.