Efficacy and Safety of Isavuconazole in the Treatment of Invasive Fungal Disease in Patients with Hematological Disorders

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Introduction: Invasive fungal infections (IFIs) are a significant contributor to morbidity and mortality in hematological malignancies (HM) patients and stem cell transplant (SCT) recipients. The FDA approved Isavuconazole (ISA) as a primary treatment for invasive aspergillosis and mucormycosis. This study aims to investigate the practical application of Isavuconazole in patients with hematological malignancies (HM) and assess their clinical outcomes and safety profiles. Patients & methods: We conducted a retrospective study of patients with probable or possible mold infections who were treated with isavuconazole for a period of at least 10 days between May 2022 and May 2024. A total of 67 patients were included in the study, 20 of whom were receiving chemotherapy, and 47 who had undergone hematopoietic stem cell transplantation (HSCT). Of these, 44 were male and 23 were female, with a median age of 48 years (ranging from 34.5 to 52). Clinical and radiological assessments were carried out at baseline and at 6 and 12 weeks of follow-up. Results: The overall success rate was 51% (CR of 30% and PR of 21%) at 6 weeks, 75% (CR of 46% and PR of 28%) at 12 weeks. The 100-day all-cause mortality rate was 19.1%[8.71-28.3%]. Multivariate logistic regression analysis showed that persistent neutropenia, male sex and Invasive Mucormycosis were independently associated with inferior responses to ISA. Isavuconazole was used as monotherapy in 22% of the cases and in combination in 78%. Adverse events potentially related to isavuconazole were reported in three patients (4%), two of whom exhibited elevated creatinine levels, and one patient who exhibited a rash associated with isavuconazole . ISV was employed as the 1st line therapy in 16 (24%) patients and as a subsequent therapy in 51 (76%) patients. Conclusion: This study provides encouraging data regarding the efficacy and safety of ISA in HM patients. Neutropenia, male sex, Invasive Mucormycosis are possibly associated with inferior responses to ISA therapy.

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