Real-world overall survival comparison between first-line Bruton tyrosine kinase inhibitors in treating chronic lymphocytic leukemia/small lymphocytic lymphoma: An analysis of Veterans Health Administration data
Journal of Managed Care & Specialty Pharmacy, 2025
Background
Three covalent Bruton's tyrosine kinase inhibitors (BTKis) are approved first-line (1L) treatments for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). However, limited real-world data, especially in veterans, evaluate long-term outcomes associated with the different BTKis.
Objective
To describe and compare real-world overall survival (rwOS) among patients with CLL/SLL treated with BTKis in the Veterans Health Administration electronic medical record database.
Methods
This was a retrospective cohort study of patients with CLL/SLL who initiated 1L monotherapy of ibrutinib, acalabrutinib, or zanubrutinib between November 2019 and September 2023. Patients were grouped into 3 cohorts based on the BTKi initiated: (1) ibrutinib, (2) acalabrutinib, or (3) acalabrutinib or zanubrutinib (given small sample initiating zanubrutinib). Key inclusion criteria were 1L monotherapy treatment with a BTKi, at least 2 diagnoses of CLL/SLL, and continuous enrollment at least 12 months prior to and at least 28 days after the initiation of the BTKi. rwOS comparing the BTKi cohorts was analyzed using Kaplan-Meier methodology and adjusted Cox proportional hazards models. Sensitivity analyses adjusting for different sets of covariates were conducted.
Results
The study included samples of 1,059, 504, and 612 patients treated with ibrutinib, acalabrutinib, and acalabrutinib or zanubrutinib (108 received zanubrutinib), respectively. Median rwOS was not reached in any cohort. In the main analysis comparing the ibrutinib and acalabrutinib cohorts, after adjustment for baseline characteristics, treatment with acalabrutinib was associated with an increased risk of death compared with ibrutinib (hazard ratio [HR], 1.33; 95% CI, 1.01-1.76; P = 0.042). In the main analysis comparing the ibrutinib and acalabrutinib or zanubrutinib cohorts, the adjusted risk of death was numerically higher for acalabrutinib- or zanubrutinib-treated patients compared with ibrutinib (HR, 1.32; 95% CI, 1.00-1.74; P = 0.050). For both comparisons, sensitivity analyses indicated similar trends in rwOS.
Conclusions
As new therapies emerge, this study highlights the comparative effectiveness of BTKis in the real world, potentially informing current clinical practice.
Authors
Fitzgerald L, Ghosh S, Khan W, Bokun A, Lax A, Mu F, Cook EE, Chen J, Chen G, Wu E, Lin Y, Shi L, Qureshi ZP, Graf SA