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.