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Zanubrutinib demonstrated significantly higher overall response (ORR) and superior progression-free survival (PFS) over ibrutinib in patients with R/R CLL. This PFS benefit was reported across all major subgroups, including the del(17p)/5NOK³³⁺ population. Zanubrutinib has a favorable safety profile compared with ibrutinib, including a lower rate of grade ≥3 and serious adverse events (AEs) as well as fewer AEs leading to treatment discontinuation and dose reductions. Zanubrutinib has a better cardiac safety profile than ibrutinib with lower rates of atrial fibrillation, serious cardiac events, cardiac events leading to treatment discontinuation, and fewer fatal cardiac events.