1624. Hepatic Safety of Isavuconazole Compared with Voriconazole in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation Complicated by Invasive Mold Disease – A Post-Hoc Analysis from the SECURE Study
Session: Poster Abstract Session: Mycology - There's a Fungus Among Us: Treatment
Friday, October 28, 2016
Room: Poster Hall
Posters
  • Hepatic Safety poster_UPLOAD.pdf (128.2 kB)
  • Background:Patients undergoing allogeneic stem cell transplantation (allo-SCT) often require mold-active antifungal treatment and are at increased risk of drug-related hepatotoxicity. We compared hepatic toxicity profiles of isavuconazole (ISAV) and voriconazole (VRC) in a post-hoc analysis of patients in the SECURE study with and without allo-SCT.

    Methods:Patients were randomized 1:1 to ISAV or VRC; allo-SCT was a stratification factor. The number of patients with treatment emergent adverse events (TEAEs) in the System Organ Class “Hepatobiliary disorders” (MedDRA v12.1) and alanine/aspartate aminotransferase (ALT/AST) and bilirubin elevation rates at the end of treatment were compared.

    Results: Of 516 patients, 20% had allo-SCT (ISAV n=54, VRC n=51). Hepatobiliary TEAEs and transaminase/bilirubin levels results are summarized in Table A. For ISAV the proportion of patients with or without allo-SCT who experienced ≥1 hepatobiliary TEAE was comparable (p=0.6); this rate was higher for patients on VRC (p=0.056). Fewer patients experienced drug-related hepatobiliary TEAEs with ISAV than VRC, both in patients with and without allo-SCT (p<0.01).

    Conclusion:In this analysis allo-SCT recipients had an increased rate of hepatobiliary toxicity. ISAV had a favorable hepatic safety profile vs VRC in patients with or without allo-SCT with a more pronounced safety benefit in patients after allo-SCT.

    Table A

     

    Without allogeneic SCT

    With allogeneic SCT

     

    ISAV

    n=203

    VRC

    n=208

    Differencea
    % (95%CL)

    Relative Riskb

    ISAV

    n=54

    VRC

    n=51

    Differencea
    % (95%CL)

    Relative Riskb

    Patients with ≥1 Hepatobiliary TEAE, n (%)

     

     

     

     

     

     

     

     

    Overall

    17 (8)

    29 (14)

    –6 (–12, 1)

    0.6

    6 (11)

    13 (25)

    –14 (–31, 2)

    0.4

    Moderate/severe

    13 (6)

    20 (10)

    –3 (–9, 3)

    0.7

    4 (7)

    8 (16)

    –8 (–23, 6)

    0.5

    Leading to permanent discontinuation

    1 (0.5)

    3 (1)

    –1 (–3, 1)

    0.3

    0

    3 (6)

    –6 (–14, 3)

    -

    Drug-related

    4 (2)

    17 (8)

    –6 (–11, −2)

    0.2

    1 (2)

    9 (18)

    −16 (−29, 3)

    0.1

    Serious

    2 (1)

    3 (1)

    −1 (−3, 2)

    0.7

    1 (2)

    3 (6)

    −4 (−13, 5)

    0.3

    Transaminase elevations >3x ULN, n/N (%)

    ALT

    6/196 (3)

    10/205 (5)

    −2 (−6, 3)

    0.6

    3/54 (6)

    7/50 (14)

    –8 (–22, 5)

    0.4

    ALT or AST

    8/196 (4)

    20/205 (10)

    –6 (–11, 0)

    0.4

    3/54 (6)

    7/50 (14)

    –8 (–22, 5)

    0.4

    ALT or AST and bilirubin 2x ULN

    0/195

    2/205 (1)

    –2 (–4, 1)

    -

    1/54 (2)

    5/50 (10)

    –6 (–17, 4)

    0.2

    a(ISAV−VRC)

    b(ISAV/VRC)

    ULN: upper limit of normal

    Werner J. Heinz, MD1, Oliver Cornely, MD, FACP, FIDSA, FAAM2, Dominik Selleslag, MD3, Galia Rahav, MD4, Michael Giladi, MD5, Mickael Aoun, MD6, Raoul Herbrecht, MD7, Andrew J. Ullmann, MD1, Nkechi Azie, MD8, Laura Kovanda, BA8, Achim Kaufhold, MD9, Marc Engelhardt, MD9 and Johan Maertens, MD, PhD10, (1)University of Würzburg Medical Center, Würzburg, Germany, (2)University Hospital of Cologne, Cologne, Germany, (3)A.Z. Sint-Jan, Brugge, Belgium, (4)Sheba Medical Center, Tel Hashomer, Israel, (5)Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, (6)Institut Jules Bordet, Brussels, Belgium, (7)University of Strasbourg, Strasbourg, France, (8)Astellas Pharma Global Development, Inc., Northbrook, IL, (9)Basilea Pharmaceutica International Ltd., Basel, Switzerland, (10)U.Z. Leuven, Leuven, Belgium

    Disclosures:

    W. J. Heinz, Astellas: Investigator , Scientific Advisor and Speaker's Bureau , Speaker honorarium
    Basilea: Investigator , Scientific Advisor and Speaker's Bureau , Speaker honorarium
    Gilead: Investigator , Scientific Advisor and Speaker's Bureau , Speaker honorarium
    Merck/MSD: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Grant recipient , Research grant and Speaker honorarium
    Pfizer: Grant Investigator , Investigator , Scientific Advisor and Speaker's Bureau , Grant recipient , Research grant and Speaker honorarium

    O. Cornely, Astellas: Consultant , Grant Investigator , Research Contractor and Speaker's Bureau , Consulting fee , Grant recipient , Research support and Speaker honorarium
    Basilea: Consultant , Grant Investigator , Research Contractor and Speaker's Bureau , Consulting fee , Grant recipient , Research support and Speaker honorarium
    Gilead: Consultant , Grant Investigator , Research Contractor and Speaker's Bureau , Consulting fee , Grant recipient , Research support and Speaker honorarium
    Merck/MSD: Consultant , Grant Investigator , Research Contractor and Speaker's Bureau , Consulting fee , Grant recipient , Research support and Speaker honorarium
    Pfizer: Consultant , Grant Investigator , Research Contractor and Speaker's Bureau , Consulting fee , Grant recipient , Research support and Speaker honorarium
    3M: Grant Investigator and Research Contractor , Grant recipient and Research support
    Actelion: Grant Investigator and Research Contractor , Grant recipient and Research support
    AstraZeneca: Grant Investigator and Research Contractor , Grant recipient and Research support
    Bayer: Grant Investigator and Research Contractor , Grant recipient and Research support
    Celgene: Grant Investigator and Research Contractor , Grant recipient and Research support
    Cubist/Optimer: Grant Investigator and Research Contractor , Grant recipient and Research support
    Duke University (NIH UM1AI104681): Grant Investigator and Research Contractor , Grant recipient and Research support
    Genzyme: Grant Investigator and Research Contractor , Grant recipient and Research support
    GSK: Grant Investigator and Research Contractor , Grant recipient and Research support
    Leeds University: Grant Investigator and Research Contractor , Grant recipient and Research support
    Miltenyi: Grant Investigator and Research Contractor , Grant recipient and Research support
    NanoMR: Grant Investigator and Research Contractor , Grant recipient and Research support
    Quintiles: Grant Investigator and Research Contractor , Grant recipient and Research support
    Scynexis: Grant Investigator and Research Contractor , Grant recipient and Research support
    The Medicine Company: Grant Investigator and Research Contractor , Grant recipient and Research support
    Viropharma: Grant Investigator and Research Contractor , Grant recipient and Research support
    Amplyx: Consultant , Consulting fee
    Anacor: Consultant , Consulting fee
    Cidara: Consultant , Consulting fee
    Da Volterra: Consultant , Consulting fee
    Daiichi Sankyo: Consultant , Consulting fee
    F2G: Consultant , Consulting fee
    Matinas: Consultant , Consulting fee
    MedPace: Consultant , Consulting fee
    Merck Serono: Consultant , Consulting fee
    Sanofi Pasteur: Consultant , Consulting fee
    Scynexis: Consultant , Consulting fee
    Seres: Consultant , Consulting fee
    Summit: Consultant , Consulting fee
    Vical: Consultant , Consulting fee
    Vifor: Consultant , Consulting fee

    D. Selleslag, Pfizer: Investigator , Educational grant and Speaker honorarium
    Basilea: Investigator , Payment for study

    G. Rahav, MSD: Consultant , Consulting fee , Educational grant and Speaker honorarium
    Pfizer: Consultant , Consulting fee , Educational grant and Speaker honorarium

    M. Giladi, None

    M. Aoun, Astellas: Investigator , Payment for study
    Basilea: Investigator , Payment for study

    R. Herbrecht, Pfizer: Board Member and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
    Astellas: Board Member , Consulting fee
    Basilea: Board Member , Consulting fee and Speaker honorarium
    Gilead: Board Member and Speaker's Bureau , Consulting fee and Speaker honorarium
    MSD: Board Member , Consulting fee

    A. J. Ullmann, Astellas: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    Basilea: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    Gilead: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    MSD: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    Pfizer: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium

    N. Azie, Astellas: Employee , Salary

    L. Kovanda, Astellas: Employee , Salary

    A. Kaufhold, Basilea: Employee , Salary and Stock options

    M. Engelhardt, Basilea: Employee , Salary

    J. Maertens, Astellas: Consultant , Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
    MSD: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium
    Gilead: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee and Speaker honorarium

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.