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Comparative Study
. 2026 Feb;32(2):186-200.
doi: 10.18553/jmcp.2025.25169. Epub 2025 Dec 3.

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

Lindsey Fitzgerald  1   2 , Sabyasachi Ghosh  3 , Wasiulla Khan  3 , Alex Bokun  3 , Angela Lax  4 , Fan Mu  4 , Erin E Cook  4 , Jingyi Chen  4 , Grace Chen  4 , Eric Wu  4 , Yilu Lin  5   6 , Lizheng Shi  5   6 , Zaina P Qureshi  3 , Solomon A Graf  7   8   9
Affiliations
Comparative Study

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

Lindsey Fitzgerald et al. J Manag Care Spec Pharm. 2026 Feb.

Abstract

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.

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Conflict of interest statement

L.F., Y.L., and L.S. have no conflict of interest to disclose. S.G., W.K., A.B., and Z.P.Q. are employees of Janssen Scientific Affairs, a Johnson & Johnson Company. S.G. also owns stocks of biotech companies and has received travel-related expenses paid by Sage Therapeutics. A.L., F.M., E.C., J.C., G.C., and E.W. are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to the sponsors in connection with the development of this manuscript. S.A.G. has received institutional research funding from Janssen Pharmaceuticals, TG Therapeutics, Acerta Pharma/AstraZeneca, BeiGene, Loxo/Lilly, and Genentech.

This study was funded by Janssen Scientific Affairs, a Johnson & Johnson Company. The study sponsor was involved in several aspects of the research, including the study design, interpretation of data, writing of the manuscript, and the decision to submit the report for publication.

The contents do not represent the views of the US Department of Veterans Affairs or the US Government.

Figures

FIGURE 1
FIGURE 1
CLL/SLL Sample Selection Flowchart Among VA Patients
FIGURE 2
FIGURE 2
Overall Survival Among Patients With CLL/SLL Treated With 1L Ibrutinib Monotherapy vs Acalabrutinib Monotherapy
FIGURE 3
FIGURE 3
Cox Proportional Hazards Models
See this image and copyright information in PMC

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