415. Breakthrough Invasive Fungal Infections in Adult Hematologic Malignancy Patients Receiving Isavuconazole Prophylaxis
Session: Poster Abstract Session: Fungal Disease: Management and Outcomes
Thursday, October 4, 2018
Room: S Poster Hall

Background: Isavuconazole (ISA) is a novel triazole antifungal approved for treating invasive aspergillosis and mucormycosis. While ISA is increasingly used for prophylaxis in hematologic malignancy patients when other azoles are contraindicated, there are currently limited data on breakthrough invasive fungal infection (IFI) rates in this context.

Methods: We retrospectively reviewed inpatient and outpatient pharmacy records from 3/2015-4/2018 to identify adult patients with hematologic malignancy who received at least 7 days of ISA for prophylaxis. Breakthrough IFI was defined by EORTC-MSG criteria.

Results: We identified 73 hematologic malignancy patients who received ISA; 29 received at least 7 days ISA for prophylaxis in 33 separate episodes. Of these patients, 52% had acute myeloid leukemia, 14% had acute promyelocytic leukemia, 10% had myelodysplastic syndrome, and 21% had another malignancy. Eighty-six percent of patients were neutropenic (median duration 24 days; range 2-213). Median duration of ISA prophylaxis was 61 days (range 8-635). The most common reason for choosing ISA over other antifungal agents was QTc prolongation (45%), followed by intolerance of other antifungals (27%) and drug-drug interactions with other azoles (21%). Four patients (12%) developed proven or probable breakthrough IFI (Table 1). Among patients with breakthrough IFI, mortality was 50% at 12 weeks.

Table 1. Characteristics of breakthrough IFI among hematologic malignancy patients receiving ISA prophylaxis.

Age/

Gender

Disease

IFI site

Organism

Diagnostic Test

ANC

Nadir

Neutropenia Duration (days)

Duration ISA (days)

Outcome (12 weeks)

32M

AML

Lung

Aspergillus fumigatus

BAL: fungal culture

<10

118

38

Death

65M

Aplastic anemia

Blood, lung

Scedosporium apiospermum

Blood culture

<100

14

13

Death

44F

ALL

Lung

Aspergillus nigri

Lung FNA: PCR, path

0

143

52

Partial response

63F

AML

Lung

Unknown*

Lung FNA negative

110

90

73

Partial response

*Probable IFI; other 3 cases were proven

Conclusion: We demonstrate a 12% rate of breakthrough IFI among hematologic malignancy patients on ISA prophylaxis, similar to published rates (10-15%) on posaconazole prophylaxis. Further study is needed to characterize risk factors for and epidemiology of ISA breakthrough.

 

Catherine DeVoe, MD1, Monica Fung, MD, MPH2, Brian Schwartz, MD2, Sarah B. Doernberg, MD3, Mimi Lo, PharmD4, Larissa Graff, PharmD4, Marisela Tan, PharmD4, Aaron Logan, MD, PhD5, Jennifer Babik, MD, PhD6 and Peter Chin-Hong, MD2, (1)Division of Hospital Medicine, University of California, San Francisco, San Francisco, CA, (2)Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA, (3)Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, (4)University of California, San Francisco, San Francisco, CA, (5)Hematology Oncology, University of California, San Francisco, San Francisco, CA, (6)Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, CA

Disclosures:

C. DeVoe, None

M. Fung, None

B. Schwartz, None

S. B. Doernberg, Genentech: Consultant , Consulting fee . Actelion: Consultant , Consulting fee .

M. Lo, None

L. Graff, None

M. Tan, None

A. Logan, None

J. Babik, None

P. Chin-Hong, None

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