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


Authors: Bogler, Y.; Stern, A.; Su, Y.; Lee, Y. J.; Seo, S. K.; Shaffer, B.; Perales, M. A.; Papanicolaou, G. A.; Neofytos, D.
Article Title: Efficacy and safety of isavuconazole compared with voriconazole as primary antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients
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. Lay Summary: When compared to voriconazole, isavuconazole is a safer and as effective primary antifungal prophylaxis during the first 3 months after allogeneic hematopoietic cell transplant, with lower rates of hepatotoxicity, and similar rates of fungal infections and all-cause mortality. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.
Keywords: prophylaxis; voriconazole; invasive fungal infections; allogeneic hematopoietic cell transplant; isavuconazole
Journal Title: Medical Mycology
Volume: 59
Issue: 10
ISSN: 1369-3786
Publisher: Oxford University Press  
Date Published: 2021-10-01
Start Page: 970
End Page: 979
Language: English
DOI: 10.1093/mmy/myab025
PUBMED: 34036319
PROVIDER: scopus
PMCID: PMC8487767
DOI/URL:
Notes: Article -- Export Date: 2 November 2021 -- Source: Scopus
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MSK Authors
  1. Susan Seo
    122 Seo
  2. Yeon Joo Lee
    50 Lee
  3. Miguel-Angel Perales
    940 Perales
  4. Brian Carl Shaffer
    173 Shaffer
  5. Yiqi Su
    20 Su
  6. Anat Stern
    13 Stern
  7. Yael Bogler
    3 Bogler