Methods: We conducted a retrospective review of adults with hematologic malignancies and HCT recipients who received ≥7 days of uninterrupted ISA primary prophylaxis between 9/1/2016 and 9/31/2017. Breakthrough IMIs were documented through chart review and classified as probable or proven according to standard criteria. The study was approved by the OHSU IRB.
Results: 135 patients received 184 courses of ISA prophylaxis for AML (N=100), GVHD (N=36), “high risk HCT” (≥14 days neutropenia immediately prior to HCT; N=25), and other indications (N=23). 10 cases of proven/probable breakthrough IMIs were identified (Invasive Pulmonary Aspergillosis (IPA) =6, Mucorales=2, Fusarium=2). 4 cases of breakthrough IPA occurred during prophylaxis for AML, and 2 occurred during prophylaxis after high-risk HCT. All breakthrough IPA occurred during prolonged neutropenia (median 46 days, range 16-181). The median duration of ISA prophylaxis prior to breakthrough IPA was 15 days (range 10-37). The median serum ISA trough level at breakthrough IPA was 3.7 mcg/mL (range 3.1-6.3). During this same time period there was no breakthrough IPA during 101 courses of voriconazole or posaconazole (POS) prophylaxis in similar patients. Only 1 case of breakthrough IPA occurred during 244 courses of POS prophylaxis in the 18 months prior to the introduction of ISA prophylaxis. Due to the higher than expected rate of breakthrough IPA, POS replaced ISA as first-line primary prophylaxis in 10/2017. Since then there have been no cases of breakthrough IPA on POS prophylaxis.
Conclusion: Our institutional experience indicates that additional studies are needed to determine the role of ISA for prophylaxis in certain high-risk hematologic malignancy patients.
M. Hakki, None