Therapeutic strategies in chronic lymphocytic leukemia: efficacy and safety of zanubrutinib in patients with arrhythmias and hemorrhagic risk. Report of two cases

The management of chronic lymphocytic leukemia (CLL) has evolved significantly with the introduction of Bruton’s tyrosine kinase inhibitors (BTKis). Zanubrutinib, a next-generation BTKi, was engineered to provide greater selectivity and reduce “off-target” effects, owing to its pharmacokinetic/pharmacodynamic profile, which offers an improved safety and efficacy profile. This report presents two illustrative cases from the ALPINE study (NCT03734016), highlighting the safety profile of zanubrutinib in CLL patients with high cardiovascular and bleeding risk. The first, a 67-year-old male with a history of atrial flutter and autoimmune hemolytic anemia, showed a sustained response without recurrence of arrhythmias or significant bleeding events despite baseline hypertension and concomitant medications. The second, a 61-year-old male with Factor V Leiden-associated thrombophilia, previous thrombotic events, and multiple comorbidities, experienced effective control of CLL without hemorrhagic complications after appropriate management of anticoagulant medication. These cases underscore the efficacy and tolerability of next-generation BTKi zanubrutinib, reinforcing its potential as a therapeutic option in complex patients with cardiovascular risk.