Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience.

Abstract

BACKGROUND\nThere are limited real-life data on isavuconazole prophylaxis and treatment of invasive mold infections (IMI) in hematological patients and allogeneic hematopoietic cell transplant (HCT) recipients.\n\n\nOBJECTIVES\nPrimary objective was to describe the indications of real-life isavuconazole administration at a university hospital. Secondary objectives included the description of liver function tests and QTc interval between baseline and end of treatment (EOT), clinical outcomes and breakthrough IMI by the EOT.\n\n\nPATIENTS/METHODS\nThis was a 5-year single-center retrospective study of all adult patients with acute myeloid leukemia and/or allogeneic HCT recipients who received isavuconazole as prophylaxis and/or treatment between June 1, 2016, and July 31, 2020.\n\n\nRESULTS\nAmong 30 identified patients, the indications for isavuconazole administration were adverse events associated with prior antifungal treatment (N: 18, 60%: hepatotoxicity, renal insufficiency, long QTc interval, neurotoxicity, and potential drug-drug interactions in 6, 4, 3, 1 and 4 patients, respectively), clinical efficacy (N: 5, 16.6%), and other reasons (N: 10, 33.3%; 5/10 patients treated with isavuconazole to facilitate hospital discharge with orally administered appropriate treatment). Alanine aminotransferase significantly decreased from baseline (mean: 129\xa0IU/L, range: 73, 202) to a mean of 48\xa0IU/L (range: 20, 80) by day 14 (P-value: 0.02), 23.5\xa0IU/L (range: 20, 27) by day 28 (P-value: 0.03) and 16.5\xa0IU/L (range: 16, 17) by day 42 (P-value: 0.009). The QTc interval decreased from baseline (mean: 456.8\xa0ms, range: 390, 533) to EOT (mean: 433.8\xa0ms, range: 400, 472; P-value: 0.03). The mean isavuconazole plasma concentration was 2.9\xa0mg/L (range: 0.9, 6.7). There was no breakthrough IMI observed.\n\n\nCONCLUSION\nIsavuconazole is a safe and reliable antifungal agent in complex hematological patients, with relatively low hepatotoxicity and QTc interval shortening properties.