Logo image
Back
CLL-1316: Comparative Cardiovascular and Infectious Safety of Acalabrutinib Versus Zanubrutinib in Chronic Lymphocytic Leukemia: A Propensity Score–Matched Real-World Analysis of the TriNetX Global Collaborative Network
Abstract   Peer reviewed

CLL-1316: Comparative Cardiovascular and Infectious Safety of Acalabrutinib Versus Zanubrutinib in Chronic Lymphocytic Leukemia: A Propensity Score–Matched Real-World Analysis of the TriNetX Global Collaborative Network

Ali Mohsin, Faiza Khan, Muhammad Furqan, Hafiz Muhammad Majid Ilyas, Hasan Ilyas, Ishtiaq Ahmad, Muhammad Usman Haider, Haider Bin Khalid, Ghulam Mustafa Mahmood, Ghazia Rehman, …
Clinical lymphoma, myeloma and leukemia, Vol.26(Suppl 1), pp.S641-S642
08/2026
DOI: 10.1016/S2152-2650(26)02104-X

View Online

Abstract

Background: Acalabrutinib and zanubrutinib are Bruton tyrosine kinase (BTK) inhibitors widely used in chronic lymphocytic leukemia (CLL), both developed to improve upon the cardiovascular toxicity profile of ibrutinib. However, direct real-world comparative safety data between these agents remain limited. This study evaluated cardiovascular and infectious outcomes following initiation of acalabrutinib versus zanubrutinib. Methods: Using the TriNetX Global Collaborative Network, we identified adults with CLL (ICD-10: C91.10, C91.12) not in remission or in relapse who initiated either BTK inhibitor. Patients with diffuse large B-cell lymphoma were excluded to minimize Richter transformation as a confounding factor. One-to-one propensity score matching balanced the cohorts according to age, sex, race, neoplasm diagnosis, and prior chemotherapy and antineoplastic medication use. Outcomes were assessed at 1, 3, 6, and 12 months. Primary outcomes included atrial fibrillation/flutter, hypertension, heart failure, ischemic stroke, hemorrhage, and serious infections (pneumonia, other respiratory infections, sepsis, urinary tract infections). Time-to-event analyses used Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. Results: Before matching, 4544 patients who received acalabrutinib and 2429 who received zanubrutinib were identified. Propensity score matching yielded 2400 patients per arm, balanced for baseline characteristics. Mean patient age was approximately 72 years, 63% of patients were male, and 80% were White. No statistically significant differences were observed for any primary outcome across all time points. Atrial fibrillation rate (1-year HR, 1.03; 95% CI, 0.89–1.19; P = 0.68), heart failure incidence (HR, 1.06; 95% CI, 0.90–1.26; P = 0.50), and risk of serious infections (HR, 1.06; 95% CI, 0.94–1.18; P = 0.34) were comparable between groups. Hypertension showed a numerical trend favoring acalabrutinib that did not reach statistical significance (884 vs 930 events; HR, 0.93; 95% CI, 0.85–1.02; P = 0.13). A near-significant hemorrhage signal favoring acalabrutinib emerged at 6 months (75 vs 99 events; HR, 0.74; 95% CI, 0.55–1.01; P = 0.053) but was attenuated at 1 year (HR, 0.84; 95% CI, 0.66–1.06; P = 0.14). Stroke HRs consistently favored acalabrutinib, without reaching statistical significance (1-year HR, 0.89; 95% CI, 0.94–1.18; P = 0.55). Conclusion: Acalabrutinib and zanubrutinib demonstrated broadly comparable cardiovascular and infectious safety profiles through 1 year. CI: confidence interval, HR: hazard ratio, ICD-10: International Classification of Diseases, Tenth Revision.
 acalabrutinib cardiovascular CLL infection zanubrutinib

Details

Metrics

1 Record Views
Logo image