Yael Bogler1, Anat Stern1, Yiqi Su1, Yeon Joo Lee1,2, Susan K Seo1,2, Brian Shaffer2,3, Miguel-Angel Perales2,3, Genovefa A Papanicolaou1,2, Dionysios Neofytos4. 1. Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. Department of Medicine, Weill Cornell Medical College, New York, NY, USA. 3. Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 4. Infectious Disease Service, Geneva University Hospital, Geneva, Switzerland.
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.
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.
Authors: Oliver A Cornely; Johan Maertens; Drew J Winston; John Perfect; Andrew J Ullmann; Thomas J Walsh; David Helfgott; Jerzy Holowiecki; Dick Stockelberg; Yeow-Tee Goh; Mario Petrini; Cathy Hardalo; Ramachandran Suresh; David Angulo-Gonzalez Journal: N Engl J Med Date: 2007-01-25 Impact factor: 91.245
Authors: Andrew J Ullmann; Jeffrey H Lipton; David H Vesole; Pranatharthi Chandrasekar; Amelia Langston; Stefano R Tarantolo; Hildegard Greinix; Wellington Morais de Azevedo; Vijay Reddy; Navdeep Boparai; Lisa Pedicone; Hernando Patino; Simon Durrant Journal: N Engl J Med Date: 2007-01-25 Impact factor: 91.245
Authors: Lauren Fontana; David S Perlin; Yanan Zhao; Brie N Noble; James S Lewis; Lynne Strasfeld; Morgan Hakki Journal: Clin Infect Dis Date: 2020-02-14 Impact factor: 9.079
Authors: I Amigues; N Cohen; D Chung; S K Seo; C Plescia; A Jakubowski; J Barker; Genovefa A Papanicolaou Journal: Biol Blood Marrow Transplant Date: 2009-10-09 Impact factor: 5.742
Authors: D Przepiorka; D Weisdorf; P Martin; H G Klingemann; P Beatty; J Hows; E D Thomas Journal: Bone Marrow Transplant Date: 1995-06 Impact factor: 5.483
Authors: Julian Lindsay; Jad Othman; Yvonne Kong; Annie Yip; Sebastiaan Van Hal; Stephen Larsen; Christian Bryant; John Gibson; Ian Kerridge; Keith Fay; William Stevenson; Chris Arthur; Sharon C A Chen; David C M Kong; Matthew Greenwood; Steven A Pergam; Catherine Liu; Monica A Slavin Journal: Open Forum Infect Dis Date: 2021-11-23 Impact factor: 4.423