Real-World Treatment Patterns and Outcomes of Zanubrutinib and Acalabrutinib in Patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma at University of California Academic Health Centers: A Retrospective Cohort Study

The second-generation Bruton tyrosine kinase inhibitors (BTKis) zanubrutinib and acalabrutinib have improved outcomes in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) patients but comparative evidence is limited. This study assessed treatment patterns and clinical outcomes among patients with CLL/SLL initiating zanubrutinib or acalabrutinib in diverse real-world healthcare settings. Adults with CLL/SLL receiving zanubrutinib or acalabrutinib monotherapy within the University of California Health system (01/01/2021–11/30/2025) were eligible. Baseline characteristics and treatment patterns were analyzed descriptively. Real-world time to treatment discontinuation (TTD), time to next treatment (TTNT), and overall survival (OS) were analyzed using Kaplan–Meier methods and univariate Cox models. The adjusted impact of sociodemographic and clinical factors on time-to-event outcomes was assessed using multivariate Cox models. In an exploratory subgroup analysis, a large language model (LLM) was used to extract adverse events (AEs) and reasons for BTKi discontinuation from unstructured electronic health records. A total of 481 patients were included (zanubrutinib cohort, n = 175; acalabrutinib cohort, n = 306). Median follow-up was 30.7 months. Median TTD was significantly longer in patients receiving zanubrutinib than in those on acalabrutinib (31.8 vs. 14.4 months; P = 0.002). Differences in TTD were statistically significant in unadjusted (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.51–0.86) and adjusted (HR 0.74, 95% CI 0.56–0.98) analyses. TTNT and OS did not significantly differ between treatments; however, trends favored zanubrutinib for both measures. In multivariate analyses, TTNT and OS were significantly shorter with increasing comorbidity burden. Overall, AE rates (grades unspecified) were similar between BTKis. Fatigue, bruising, and rash were significantly more common in the zanubrutinib cohort, and headache was significantly more common in the acalabrutinib cohort. The most common reasons for discontinuation of both BTKis were AEs and disease progression. Patients with CLL/SLL remained on treatment longer with zanubrutinib than with acalabrutinib. Further investigation into factors underlying differences in treatment patterns and outcomes with zanubrutinib and acalabrutinib is warranted to optimize treatment strategies.