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

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).

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.

In total, 2,163 patients (81.4% in 1L and 18.6% in 2L+) were identified with a mean age of 73.8 $\pm$ 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.

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.