Dingli, D., De Nigris, E., Leng, S., Farooqui, M. Z. H., Yapici, H. O., Weimer, I., Jiao, W., Hyatt, H., Zhang, X., Lodaya, K., & Obeng-Kusi, M. (2026). Real-world cardiac events and outcomes in cBTKi-treated chronic lymphocytic leukemia patients. Future oncology (London, England), 22(1), 71–82. https://doi.org/10.1080/14796694.2025.2600913
Abstract
Aim
To evaluate the real-world incidence of cardiovascular adverse events (CVAE) and clinical outcomes among patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) treated with covalent Bruton’s Tyrosine Kinase inhibitors (cBTKis).
Methods
Patients initiating cBTKi treatment from 1 January 2020 to 1 January 2023 were identified using claims data. Demographics, first-line (1L) and second-line or later (2L+) therapy, incident CVAEs, and clinical outcomes were assessed.
Results
In total, 2,163 patients (81.4% in 1L and 18.6% in 2L+) were identified with a mean age of 73.8 ± 9.2 years and 40.6% female. The most common incident CVAEs were hypertension (23.4%), atrial fibrillation (10.2%), ventricular arrhythmias (10.1%), heart failure (8.5%), and atrial flutter (4.2%). Those with CVAEs experienced higher switching to next treatment + death and worse overall survival than those without CVAEs. Incidence rates were ~2–3 fold lower with acalabrutinib than ibrutinib for hypertension, atrial fibrillation, and atrial flutter. Kaplan-Meier estimates for the likelihood of not experiencing a CVAE were 83% (acalabrutinib) and 72% (ibrutinib) at 12-months.
Conclusions
Despite improvements in 2nd-generation cBTKi cardiotoxicity, patients with CLL/SLL receiving cBTKis have a considerable cardiovascular disease burden. These findings highlight the unmet need for CLL/SLL treatment options with improved efficacy and safety profiles.