1291 - Safety of Isavuconazole Compared with Voriconazole as Primary Antifungal Prophylaxis in Allogeneic Hematopoietic Cell Transplant Recipients

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Presenting Author(s)

Yael Bogler

Infectious Disease physician
Memorial Sloan Kettering Cancer Center
Sunnyvale, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

AS

Anat Stern

Research fellow
Memorial Sloan Kettering Cancer Center
New York, NY
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
YS

Yiqi Su

Data Analyst II
Memorial Sloan Kettering
New York, NY
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Yeon Joo Lee

Assistant Attending
Memorial Sloan Kettering Cancer Center
New York, New York
Disclosure: Ansun BioPharma (Scientific Research Study Investigator)Astellas Pharma (Scientific Research Study Investigator)
SS

Susan K. Seo

Director, Antibiotic Management Program
Memorial Sloan Kettering
New York, New York
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SG

Sergio Giralt

Dr Sergio Giralt
Memorial Sloan Kettering
New York, NY
Disclosure: Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.)
MP

Miguel-Angel Perales

Chief, associate attending medicine
Memorial Sloan Kettering Cancer Center
New York, New York
Disclosure: Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.)
DN

Dionysios Neofytos

Infectious Diseases attending
Geneva University Hospital
Geneva, Geneve, Switzerland
Disclosure: Basilea (Advisor or Review Panel member)Gilead (Advisor or Review Panel member)MSD (Advisor or Review Panel member, Research Grant or Support)Pfizer (Advisor or Review Panel member, Research Grant or Support)
Genovefa Papanicolaou

Memorial Sloan Kettering Cancer Center
New York, NY
Disclosure: Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

Background: Voriconazole (VCZ) is used as mold active primary antifungal prophylaxis (AFP) after allogenic hematopoietic cell transplant (HCT) but is frequently discontinued due to adverse events (AE), variable pharmacokinetics and drug-drug interactions. Limited data exists on the safety of Isavuconazole (ICZ) as AFP in HCT patients (pts). The study objectives were to compare 1) rates of AFP premature discontinuation (d/c), 2) changes in transaminases values from start to end of treatment (EOT) and 3) rates of invasive fungal infections (IFI) and all-cause mortality by Day (D) +180 post HCT between VCZ and ICZ AFP.

Methods: This is a matched cohort analysis of 95 pts enrolled in a clinical trial of ICZ AFP from 7/1/2017-10/31/2018 (ICZ-cohort) and 210 pts who received VCZ AFP standard of care between 9/1/2014-12/31/2015 at MSKCC (VCZ-cohort). The cohorts were matched using propensity scores (Table 1). AFP was administered for 75-100 days per institutional guidelines. Premature d/c of AFP was defined as d/c for IFI or AE by D +100 post HCT or interruption of >14 days for any reason. The cumulative incidence function and log rank test were used to compare groups. Mean transaminase values were compared using paired T-tests.Table 1. Baseline characteristics

Results: The median (Interquartile range) duration of AFP was 94 (87-100) days and 76 (23-94) days in ICZ and VCZ cohorts respectively (p< 0.0001). Premature d/c occurred in 14/95 (14.7%) of ICZ and 92/210 (43.8%) of VCZ cohorts (p< 0.0001) (Figure 1). The most common cause for AFP d/c was hepatotoxicity: ICZ-cohort: 5/95 (5.26%) vs VCZ-cohort: 48/210 (22.8%). Transaminases at EOT and up to 14 days were increased in VCZ but not ICZ cohort (Figure 2). IFI occurred in 3.15% (3/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.88) (Figure 3). In ICZ-cohort IFI included 3 Candida bloodstream infections (BSI) occurring on ICZ AFP. In VCZ-cohort IFI included one Candida BSI after VCZ d/c, and 5 probable mold infections; 3/5 with serum galactomannan > 0.5 and 2 with beta-D-glucan > 80. IFI occurred on VCZ in 1 pt and after VCZ premature d/c in 5 pts. All-cause mortality was 6.31% (6/95) in ICZ-cohort and 2.85% (6/210) in VCZ-cohort (p=0.089).Figure 1. Cumulative incidence of premature discontinuation of AFP by D+100

Figure 2. Transaminases at baseline,end of treatment (EOT), EOT +7 days and EOT +14 days in ICZ- and VCZ cohorts

Figure 3. Cumulative incidence of IFI by day +180

Conclusion: There was less premature discontinuation and hepatotoxicity with ICZ AFP, but no increase in IFI or death compared to VCZ AFP in allogeneic HCT pts.