The objective of this real–world study was to evaluate treatment persistence and treatment discontinuation associated with first–line covalent Bruton tyrosine kinase inhibitor (cBTKi) use in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

A retrospective observational cohort was identified using the US IQVIA PharMetrics® closed claims database. Adult patients with ≥2 diagnostic codes for CLL/SLL who initiated first–line cBTKi monotherapy between January 1, 2022, and February 28, 2025, were included. Patients were required to have continuous insurance enrollment for at least three months prior to treatment initiation and were followed until study end or loss to follow–up. Outcomes included treatment discontinuation (defined as time from index to regimen end date if there was a subsequent therapy, or a gap of ≥120 days between regimen end date and last activity/enrollment date) and treatment persistence (defined as the probability of a patient continuing on treatment). Time to treatment discontinuation was analyzed using Kaplan-Meier estimates. A multivariable Cox proportional hazards model adjusted for age, sex, race, ethnicity, payer type, geographic region, and Charlson Comorbidity Index and was used to estimate the hazard ratio of discontinuation between zanubrutinib and acalabrutinib or ibrutinib. A subgroup analysis was conducted in elderly patients aged ≥65 years.

A total of 1,850 patients were included, comprising 608 treated with zanubrutinib, 826 with acalabrutinib, and 416 with ibrutinib. Baseline characteristics were generally comparable across treatment groups, although patients treated with zanubrutinib were older, with a higher proportion aged ≥65 years. Median follow–up was 12 months for zanubrutinib, 14 months for acalabrutinib, and 17 months for ibrutinib. At 12 months, treatment persistence was highest with zanubrutinib (82.8%; 95% CI, 79.1–85.9), followed by acalabrutinib (78.7%; 95% CI, 75.4–81.7) and ibrutinib (68.1%; 95% CI, 62.8–72.9; P<0.0001). At 24 months, persistence remained higher with zanubrutinib (74.7%; 95% CI, 69.3–79.3) compared with acalabrutinib (66.3%; 95% CI, 61.6–70.6) and ibrutinib (58.7%; 95% CI, 52.7–64.3; P=0.0002). Multivariable analyses showed a significantly lower risk of treatment discontinuation with zanubrutinib versus acalabrutinib (adjusted hazard ratio [aHR], 0.76; 95% CI, 0.59–0.97; P=0.0257) and versus ibrutinib (aHR, 0.51; 95% CI, 0.39–0.66; P<0.0001). Similar results were observed in patients aged ≥65 years.