CNS Aspergillosis Following BTK Inhibitors Mimicking Secondary CNS Lymphoma – A Case Series (P14-13.004)

Abstract

<h3>Objective:</h3> NA <h3>Background:</h3> BTK inhibitors are commonly used in malignant B-cell lymphomas but can be associated with fungal infections, in part driven by altered platelet functions that diminish anti-fungal immune mechanisms. We describe four unique patients treated for B-cell malignancies (B-cell lymphoma, CLL, mantle cell lymphoma, and Waldenstrom’s disease) with progressive neurological deficits initially thought to represent secondary CNS lymphoma but on further diagnostic workup identified as CNS Aspergillosis. <h3>Design/Methods:</h3> Retrospective review of patients managed for B-cell hematological malignancies with BTK inhibitors associated with CNS Aspergillosis. <h3>Results:</h3> Four male patients (age 61–74) were treated with ibrutinib or zanubrutinib at a dose ranging from 160–560 mg daily (range 3–12 months) when developing new neurological symptoms and imaging findings were suggestive of recurrent lymphoma with CNS involvement. However, subsequent brain biopsies revealed invasive cerebral Aspergillosis in all cases with pulmonary involvement in three out of the four cases. Symptom presentation included headache and seizures (n=4), paresthesias (n=1) and expressive aphasia (n=1). Initial anti-fungal treatment consisted of voriconazole at a dose of 200–500 mg twice daily and subsequently posaconazole in three out of four patients. Additionally, three patients underwent surgical resection. Two patients remained stable without fungal disease progression for more than a year. One patient stopped taking voriconazole after 6 months due to side effects (decreased appetite, fatigue, lethargy, weight loss, and night sweats) and was eventually lost to follow-up. One patient had recurrent Aspergillosis and passed away following antifungal treatment for over two years. <h3>Conclusions:</h3> BTK inhibitors can be associated with fungal infections, including CNS involvement. These four cases illustrate the challenge in establishing a correct diagnosis and highlight the importance of considering atypical and fungal infections in individuals treated with BTK inhibitors. <b>Disclosure:</b> Ms. Murthy has nothing to disclose. The institution of Dr. Martinez-Lage has received research support from NIH. Jeremy Abramson has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Bristol-Myers Squibb. Jeremy Abramson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kite Pharma. Dr. Branagan has nothing to disclose. Dr. Ji has nothing to disclose. Yi-Bin Chen, 13609 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Incyte. Yi-Bin Chen, 13609 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Daiichi. Yi-Bin Chen, 13609 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Yi-Bin Chen, 13609 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Equilium. Yi-Bin Chen, 13609 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actinium. Yi-Bin Chen, 13609 has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celularity. Dr. Letourneau has received research support from World Health Information Science Consultants, LLC. Dr. Letourneau has received publishing royalties from a publication relating to health care. Brian Nahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Robeaute. Brian Nahed has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BK Ultrasound. Brian Nahed has stock in React Neuro. Brian Nahed has received research support from NIH. Dr. Nelson has nothing to disclose. Dr. Arrillaga-Romany has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer Ingelheim. The institution of Dr. Arrillaga-Romany has received research support from Astex Pharmaceuticals. The institution of Dr. Arrillaga-Romany has received research support from Gsk. Dr. Wang has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Seattle Genetics. The institution of Dr. Wang has received research support from Merck. Dr. Wang has received publishing royalties from a publication relating to health care. Dr. Dietrich has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Dietrich has received publishing royalties from a publication relating to health care.