Voriconazole prophylaxis in leukemic patients: A retrospective single-center study

Abstract

Background Invasive fungal infections commonly occur in acute myeloid and lymphoblastic leukemia patients receiving chemotherapy. In these patients with acute leukemia, posaconazole prophylaxis is recommended; however, voriconazole may be a less costly alternative. Objectives The objective of this study was to evaluate the efficacy and safety of voriconazole prophylaxis in acute leukemia patients. Methods A retrospective chart review of inpatients at Sunnybrook Health Sciences Centre between 2005 and 2017 was completed. Hospitalized adult acute leukemia patients who received voriconazole prophylaxis (cases) were compared to patients who received fluconazole or no prophylaxis during chemotherapy (controls). Statistical analyses comparing baseline characteristics, safety, and efficacy outcomes between the study cohorts were completed. A posaconazole literature-based weighted mean risk was compared to the voriconazole risk of invasive fungal infection identified in this study. Results Of 490 acute myeloid leukemia or acute lymphoblastic leukemia patients, 83 controls and 92 cases were eligible. Case patients received an average of 24.4 ± 10.8 days of voriconazole prophylaxis. The incidence of proven or probable invasive fungal infections with voriconazole was 3.3% (3/92) versus 7.2% (6/83) in the control cohort (p > 0.05) and was comparable to the literature reported weighted incidence of invasive fungal infection with posaconazole (2.4 ± 2.1%; 95% CI 1.3%–3.4%; p > 0.05). Voriconazole was well tolerated by patients (91%; 84/91; seven discontinued due to asymptomatic elevated liver function tests). Conclusions Voriconazole prophylaxis was found to be safe, effective, and comparable to literature-based efficacy data for risk of invasive fungal infection with posaconazole antifungal prophylaxis in patients with acute leukemia undergoing chemotherapy and could represent a significant cost advantage.

High-Risk Neutropenic Fever and Invasive Fungal Diseases in Patients with Hematological Malignancies

“…Higher rates of b-IFDs ranging between 5.8% and 8.3% were reported in AML patients receiving AFP with isavuconazole, despite fewer drug–drug interactions (DDIs) [ 50 , 51 , 52 ]. Retrospective analyses reported an incidence for b-IFDs of around 3% in patients with HM receiving AFP with voriconazole [ 53 , 54 ]. Finally, AFP with echinocandin resulted in a high rate of b-IFDs in some studies [ 55 , 56 ], but not in others [ 57 , 58 , 59 ].…”

Primary prophylaxis of invasive fungal diseases in patients with haematological malignancies: 2022 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO)

“…Several retrospective studies have recently evaluated voriconazole in patients with acute leukaemia receiving chemotherapy. 34 , 39–45 One retrospective study ( n = 175) found an incidence of bIFD of 3.3% in the voriconazole arm versus 7.2% in the fluconazole arm. 39 In another study in 241 AML patients receiving (re)induction chemotherapy, bIFD rate was 1.1% in the voriconazole arm, slightly lower than observed with either isavuconazole or posaconazole prophylaxis.…”

“… 34 , 39–45 One retrospective study ( n = 175) found an incidence of bIFD of 3.3% in the voriconazole arm versus 7.2% in the fluconazole arm. 39 In another study in 241 AML patients receiving (re)induction chemotherapy, bIFD rate was 1.1% in the voriconazole arm, slightly lower than observed with either isavuconazole or posaconazole prophylaxis. 34 A study in AML/MDS patients found that a switch to intravenous antifungals was significantly less common in those 471 patients receiving voriconazole prophylaxis (20.6%) versus those receiving fluconazole or itraconazole (30.1%).…”

Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2021

“…41 In cohort studies of AML patients, the use of voriconazole prophylaxis was associated with an IFD rate of 3-5%. 48,53,54 Due to variable metabolism, CYP2C19 testing prior to commencement could assist with dose selection (please refer to the accompanying optimising antifungal therapy and TDM guidelines by Chau et al 2021 182 , which can be found elsewhere in this supplement). 55,56 Itraconazole Since the 2014 guidelines, a new formulation of itraconazole has been introduced (see later discussion).…”