Bruton tyrosine kinase inhibitors and invasive aspergillosis and mucormycosis: a case report and multi-center exploratory retrospective study.

BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) are increasingly utilized for patients with certain malignant hematologic conditions. While cases of invasive fungal infections have been reported in patients on BTKIs, no multi-center epidemiological studies have been performed. The Epic Cosmos platform, a nationwide electronic health record data set, provides an opportunity to assess real-world epidemiologic data.

CASE SUMMARY: A 69-year-old female with recently diagnosed Waldenström macroglobulinemia with associated autoimmune hemolytic anemia undergoing treatment with zanubrutinib and prednisone presented with fatigue and acute kidney injury. Imaging demonstrated a bladder mass with bilateral hydronephrosis leading to transurethral resection of the bladder mass with histopathology revealing both broad ribbon-like hyphae resembling Mucorales spp. and acute-angle branching resembling Aspergillus spp. with angioinvasion. Additional imaging revealed bilateral pulmonary cavitary lesions and renal and brain involvement. Bronchoalveolar lavage returned a positive galactomannan and culture growth of Aspergillus fumigatus. The patient was treated with liposomal amphotericin B with eventual transition to oral isavuconazole. Zanubrutinib and steroids were discontinued. To assess real-world occurrence of IFIs in patients on BTKIs, we performed an exploratory analysis using Epic Cosmos.

CONCLUSION: IFIs continue to be described in patients undergoing treatment with BTKIs. Through exploratory analysis using Epic Cosmos, aspergillosis occurred not infrequently (0.5%-1.9%) in patients on various BTKIs. Of patients on ibrutinib with a diagnosis of chronic graft-versus-host disease, aspergillosis was identified in 32 (8.3%) patients. Patients on BTKIs who developed aspergillosis were frequently on corticosteroids. Mucormycosis in patients on BTKIs was rare (<0.1%).