A single-center, open-label trial of isavuconazole prophylaxis against invasive fungal infection in patients undergoing allogeneic hematopoietic cell transplantation Journal Article


Authors: Stern, A.; Su, Y.; Lee, Y. J.; Seo, S.; Shaffer, B.; Tamari, R.; Gyurkocza, B.; Barker, J.; Bogler, Y.; Giralt, S.; Perales, M. A.; Papanicolaou, G. A.
Article Title: A single-center, open-label trial of isavuconazole prophylaxis against invasive fungal infection in patients undergoing allogeneic hematopoietic cell transplantation
Abstract: Isavuconazole is a broad-spectrum triazole approved for treatment of invasive fungal infections (IFIs). In this open-label, single-arm study, we evaluated isavuconazole for antifungal prophylaxis after allogeneic hematopoietic cell transplantation (HCT). Adult patients admitted for first HCT received micafungin 150 mg i.v. daily from admission through day +7 (D+7) post-transplantation (±2 days) followed by isavuconazole prophylaxis (i.v./p.o. 372 mg every 8 hours for 6 doses and then 372 mg daily) through maximum D+98 post-HCT. Patients were followed through D+182. The primary endpoint was prophylaxis failure, defined as discontinuation of prophylaxis for proven/probable IFI; systemic antifungal therapy for >14 days for suspected IFI; toxicity leading to discontinuation; or an adverse event. Between June 2017 and October 2018, 99 patients were enrolled in the study, of whom 95 were included in our analysis. The median patient age was 57 years (interquartile range [IQR], 50 to 66 years). Sixty-four (67%) patients received peripheral blood, 17(18%) received bone marrow, and 14 (15%) received a cord blood allograft for acute leukemia (55%), lymphoma (17%), myelodysplastic syndrome (16%), or another hematologic disease (14%). One-third (n = 31; 33%) of patients underwent CD34+-selected HCT. Isavuconazole prophylaxis was given for a median of 90 days (IQR, 87 to 91 days). Ten patients (10.7%) met the primary endpoint. Candidemia occurred in 3 patients (3.1%), 1 of whom had grade III skin acute graft-versus-host disease (GVHD). Toxicity leading to discontinuation occurred in 7 patients (7.4%). The most common toxicity was liver function abnormalities in 5 patients, including grade 1 transaminitis in 2 patients and grade 3 hyperbilirubinemia in 3 patients. Four patients (4.2%) had early discontinuation of isavuconazole for reasons not meeting the primary study endpoint. Six patients died during the study period, including 3 during prophylaxis and 3 during follow-up. No deaths were attributed to isavuconazole. The majority (85%) of allogeneic HCT recipients completed isavuconazole prophylaxis according to protocol. The rate of breakthrough candidemia was 3.1%, and there were no invasive mold infections. Our data support the utility of isavuconazole for antifungal prophylaxis after HCT. © 2020 American Society for Transplantation and Cellular Therapy
Keywords: adult; aged; allograft; major clinical study; overall survival; clinical trial; drug tolerability; drug withdrawal; liver function; side effect; systemic therapy; methotrexate; follow up; cd34 antigen; anemia; nausea; cyclophosphamide; alanine aminotransferase blood level; aspartate aminotransferase blood level; rash; alanine aminotransferase; aspartate aminotransferase; acute graft versus host disease; acute leukemia; graft failure; myelodysplastic syndrome; prophylaxis; lymphoma; graft versus host reaction; allogeneic hematopoietic stem cell transplantation; umbilical cord blood; open study; hospital admission; hyperbilirubinemia; drug blood level; liver function test; bloodstream infection; infection prevention; vancomycin resistant enterococcus; drug substitution; tacrolimus; rapamycin; candidiasis; cyclosporine; posaconazole; voriconazole; micafungin; hematologic disease; enterococcal infection; respiratory failure; lung lesion; lung nodule; allogeneic hematopoietic cell transplantation; hepatotoxicity; posttransplant lymphoproliferative disease; bacterial pneumonia; hypertransaminasemia; esophagus candidiasis; candidemia; systemic mycosis; bronchiolitis obliterans; invasive fungal infection; epstein barr virus infection; antifungal therapy; tuberculostatic agent; antifungal prophylaxis; mycophenolate mofetil; human; male; female; article; nocardiosis; antifungal susceptibility; isavuconazole
Journal Title: Biology of Blood and Marrow Transplantation
Volume: 26
Issue: 6
ISSN: 1083-8791
Publisher: Elsevier Inc.  
Date Published: 2020-06-01
Start Page: 1195
End Page: 1202
Language: English
DOI: 10.1016/j.bbmt.2020.02.009
PUBMED: 32088367
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 1 July 2020 -- Source: Scopus
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Citation Impact
MSK Authors
  1. Susan Seo
    78 Seo
  2. Yeon Joo Lee
    32 Lee
  3. Sergio Andres Giralt
    648 Giralt
  4. Miguel-Angel Perales
    494 Perales
  5. Juliet N Barker
    267 Barker
  6. Roni Tamari
    108 Tamari
  7. Brian Carl Shaffer
    68 Shaffer
  8. Yiqi Su
    7 Su
  9. Anat Stern
    3 Stern
  10. Yael Bogler
    2 Bogler