Is Brukinsa (Zanubrutinib) a Safer Bruton’s Tyrosine Kinase (BTK) Inhibitor in Relapsed or Refractory Chronic Lymphocytic Leukemia? A Systematic Review and Meta-Analysis

Background/Objectives: Zanubrutinib (Brukinsa) is a next-generation Bruton’s tyrosine kinase inhibitor approved for the treatment of relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL); however, a comprehensive quantitative assessment of its safety profile remains limited. Methods: A systematic search of PubMed, Scopus, Web of Science, and MEDLINE was conducted to identify clinical trials published up to August 2025 that reported treatment-emergent adverse events (TEAEs) associated with zanubrutinib in patients with R/R CLL/SLL. Pooled incidence estimates were calculated using a random-effects model (DerSimonian and Laird method). Results: Four studies comprising 508 patients were included, with median follow-up durations ranging from 15.1 to 34.5 months. The pooled incidence of any-grade adverse events was 98.5% (95% CI, 97.1–99.9), while grade ≥3 adverse events occurred in 67.0% (95% CI, 55.4–78.7). Serious adverse events were reported in 32.2% of patients (95% CI, 25.1–39.3), treatment discontinuation due to toxicity occurred in 7.2% (95% CI, 2.5–11.8), and adverse event-related mortality was observed in 7.1% (95% CI, 0.2–13.9). The most frequently reported hematological adverse events were neutropenia (32.1%) and anemia (26.7%), while common non-hematological adverse events included bleeding events (51.9%), upper respiratory tract infections (27.2%), pneumonia (19.4%), and hypertension (16.4%). Atrial fibrillation occurred in 2.9% of patients. Conclusions: Zanubrutinib was associated with a high incidence of adverse events, although rates of treatment discontinuation and atrial fibrillation were relatively low, supporting its tolerability in R/R CLL/SLL within clinical trial settings while highlighting the need for continued long-term and real-world safety monitoring.