Fatal Cryptococcal Meningitis in a Patient With Chronic Lymphocytic Leukemia Treated With Ibrutinib

According to the latest World Health Organization classification published in 2022, chronic lymphocytic leukemia (CLL) is classified as a low-grade proliferation of clonal B-cells. The Bruton tyrosine kinase (BTK) pathway plays a crucial role in B-cell receptor signaling. Ibrutinib, the first irreversible BTK inhibitor, has been shown to improve the survival of CLL patients with lower toxicity than traditional chemotherapy. Cryptococcosis is an invasive fungal infection that primarily affects individuals with compromised immune systems. We present a case of a 69-year-old male with relapsed CLL who received treatment with ibrutinib and subsequently developed meningeal cryptococcosis, presenting with seizures and fever. A physical exam showed bilateral hypoacusis, but no focal deficits. Cerebral imaging was normal and laboratory results showed a low gamma globulin level and leucopenia with lymphopenia but without neutropenia. The cerebrospinal fluid profile was not inflammatory, opening pressure was normal, the classic India ink test was positive, and fungal cultures grew Cryptococcus neoformans. To complete investigations, HIV testing was negative, and sinus and chest tomography scans showed no anomalies. Treatment consisted of discontinuing ibrutinib and administering anti-fungal therapy with liposomal amphotericin (4 mg/kg/day) in combination with flucytosine (25 mg/kg/day). However, the patient's neurological status declined, and he passed away. This case highlights the potential risk of developing opportunistic infections such as cryptococcal meningitis in CLL patients treated with ibrutinib. It is crucial to consider the patient's immune status when administering ibrutinib and to closely monitor for signs of infection.