What is the clinical evidence from this study?

Study design: Cohort. Population: Chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL). Intervention: Acalabrutinib vs. Ibrutinib. Primary outcome: Likelihood of not experiencing a cardiovascular adverse event (CVAE) at 12 months.

December 19, 2025Open Access

Real-world cardiac events and outcomes in cBTKi-treated chronic lymphocytic leukemia patients

Key Result

Acalabrutinib was associated with a higher 12-month likelihood of not experiencing a cardiovascular adverse event compared to ibrutinib (83% vs 72%) in patients with CLL/SLL.

Study Design

Type

Cohort

Structured PICO

Does the choice of cBTKi (acalabrutinib vs ibrutinib) affect the incidence of cardiovascular adverse events in patients with CLL/SLL?

Population

Patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) initiating covalent Bruton's Tyrosine Kinase inhibitor (cBTKi) treatment, 40.6% female.

Intervention

Covalent Bruton's Tyrosine Kinase inhibitors (cBTKis), specifically acalabrutinib.

Comparator

Ibrutinib (first-generation cBTKi).

Outcome

Incidence of cardiovascular adverse events (CVAE) and clinical outcomes (switching to next treatment + death, overall survival).safety

Real-world data demonstrates a considerable cardiovascular disease burden in CLL/SLL patients treated with cBTKis, though second-generation agents like acalabrutinib show a significantly lower incidence of cardiotoxicity compared to ibrutinib.

Main Result

Absolute Event Rate: 83% vs 72%

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: 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.