Zanubrutinib, a New Bullet Against Chronic Lymphocytic Leukemia Even When Localized in Central Nervous System.

INTRODUCTION: Central nervous system (CNS) and extralymphatic involvement in chronic lymphocytic leukemia (CLL) is rare and associated with poor prognosis. CASE DESCRIPTION: We report the case of a 45-year-old woman with refractory CLL who developed CNS and extralymphatic lesions after three prior lines of therapy, including rituximab-bendamustine, rituximab-idelalisib, and rituximab-venetoclax. Third-line treatment with rituximab-venetoclax led to partial remission (PR), followed by a 2-month treatment-free interval before the emergence of a new lesion. Treatment with zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor (BTKi), was initiated, resulting in significant clinical improvement and near-complete resolution of lesions. DISCUSSION: Zanubrutinib's enhanced blood-brain barrier (BBB) penetration and favorable safety profile make it a promising option for CNS-CLL and also for other extralymphatic lesions. CONCLUSION: This case underscores the potential of zanubrutinib in addressing challenging CLL presentations.