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Scientific article
English

Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients

Published inMedical mycology, vol. 59, no. 10, p. 970-979
Publication date2021-10-04
Abstract

Voriconazole is frequently discontinued prematurely as primary antifungal prophylaxis (AFP) in allogeneic hematopoietic cell transplant (HCT) recipients due to adverse events. Limited data exists for isavuconazole as AFP. We analyzed adult HCT recipients who received voriconazole or isavuconazole AFP to estimate rate of premature AFP discontinuation, identify risk factors for premature AFP discontinuation, and compare incidence of invasive fungal infection (IFI) and survival at day + 180 post-HCT between patients who received voriconazole/isavuconazole-AFP. This was a propensity score matched cohort analysis of 210 HCT-recipients who received voriconazole-AFP (9/1/2014-12/31/2016; voriconazole-cohort), and 95 HCT-recipients who received isavuconazole-AFP (5/1/2017-10/31/2018; isavuconazole-cohort). AFP discontinuation for any reason prior to completion was defined as "premature". Median (interquartile range, IQR) duration of AFP was longer in the isavuconazole-cohort (94 days, 87-100) vs. the voriconazole-cohort (76 days, 23-94; P-value < 0.0001). Premature AFP discontinuation was more frequent in the voriconazole-cohort (92/210, 43.8%) vs. the isavuconazole-cohort (14/95, 14.7%; P-value < 0.0001). The most common reason for premature discontinuation was biochemical hepatotoxicity (voriconazole-cohort: 48/210, 22.8% vs. isavuconazole-cohort: 5/95, 5.26%; P-value = 0.0002). Transaminase values between baseline and end-of-treatment (EOT) and up to 14 days post-EOT significantly increased in the voriconazole-cohort, but remained unchanged in the isavuconazole-cohort. The incidence of IFI at day + 180 was 2.9% (6/210) and 3.2% (3/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.881). All-cause mortality at day + 180 was 2.4% (5/210) and 6.3% (6/95) in the voriconazole-cohort and isavuconazole-cohort, respectively (P-value = 0.089). When compared to voriconazole, isavuconazole was a safer and as effective primary AFP during the first 3 months after HCT.

eng
Keywords
  • Isavuconazole
  • Allogeneic hematopoietic cell transplant
  • Invasive fungal infections
  • Prophylaxis
  • Voriconazole
  • Animals
  • Antifungal Agents / adverse effects
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / veterinary
  • Humans
  • Nitriles
  • Pyridines
  • Retrospective Studies
  • Transplant Recipients
  • Triazoles
  • Voriconazole / adverse effects
Funding
  • NCI NIH HHS - [P30 CA008748]
Citation (ISO format)
BOGLER, Yael et al. Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients. In: Medical mycology, 2021, vol. 59, n° 10, p. 970–979. doi: 10.1093/mmy/myab025
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Article (Published version)
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ISSN of the journal1369-3786
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