The objective of the study was to assess real-world effectiveness outcomes among treatment-naive adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in the United States who initiated first-line zanubrutinib or acalabrutinib monotherapy.

This was a retrospective claims‑based analysis using data from the Komodo database between January 2015 and August 2025. Eligible patients were adults (aged ≥18 years) in the US with ≥2 diagnoses of CLL or SLL, who were treatment naive for CLL and had an index claim for monotherapy with zanubrutinib (January 2023 to August 2025) or acalabrutinib (November 2019 to August 2025). Patients were required to have evidence of healthcare activity for one year before and three months after treatment initiation. Patients with prior CLL/SLL therapy, clinical trial participation, or 2 diagnoses of mantle cell lymphoma were excluded. Endpoints assessed included overall survival (OS), measured from index claim to all‑cause mortality, and time to next treatment (TTNT), measured from index claim to initiation of subsequent therapy or death.

Among 16,788 patients included in the analysis (zanubrutinib, n=5,819; acalabrutinib, n=10,969), the median age was 73.3 years in the zanubrutinib cohort and 71.8 years in the acalabrutinib cohort. Median follow‑up was 12.8 months for zanubrutinib and 16.4 months for acalabrutinib. Median TTNT and OS were not reached in either cohort. In unadjusted analyses, zanubrutinib was associated with longer TTNT (hazard ratio [HR], 0.88; 95% CI, 0.79–0.97; P=0.009) and OS (HR, 0.72; 95% CI, 0.62–0.82; P<0.001) compared with acalabrutinib. After inverse probability of treatment weighting adjustment, zanubrutinib remained associated with improved OS (HR, 0.75; 95% CI, 0.65–0.86; P<0.001) and TTNT (HR, 0.89; 95% CI, 0.80–0.98; P=0.02).