The cardiac toll of ibrutinib: exploring atrial fibrillation in treated patients

Abstract Introduction Ibrutinib (IBT), a Bruton's tyrosine kinase inhibitor, is a targeted therapy widely used in the treatment of B-cell malignancies. While effective in improving survival outcomes, ibrutinib has been increasingly associated with cardiovascular toxicities, particularly atrial fibrillation (AF). Purpose To characterize the incidence, risk factors, and clinical outcomes of ibrutinib-induced atrial fibrillation (IRAF) in patients with hematologic malignancies. Methods A retrospective, single-center study analyzed patients treated with ibrutinib between 2010 and 2024. Demographic, clinical, and treatment data were collected. Statistical analyses were performed to identify potential predictors of AF and its impact on patient outcomes. Results Among 93 patients receiving IBT, 14 (15.1%) developed new-onset AF, with a median time to onset of 33.5 months (IQR 15-82) from therapy initiation. Patients with IRAF were older (75.6 ± 5.0 vs. 69.5 ± 10.8 years; p=0.002) and had a higher prevalence of arterial hypertension (71.4% vs. 59.5%; p=0.398) and diabetes (35.7% vs. 19.0%; p=0.172). Regarding cancer type, the majority of patients who experienced IRAF were diagnosed with chronic lymphocytic leukemia (9, 64.3%), followed by Waldenstrom's macroglobulinemia (3, 21.4%). Additionally, patients who underwent other forms of cancer therapy were significantly more likely to develop IRAF (92.8% vs. 64.6%; p=0.035) than ibrutinib as first line therapy. Ibrutinib dose did not impact the risk of developing IRAF (p=0.100). Among baseline echocardiographic parameters, left atrial volume was larger in patients who presented with IRAF (42.5 mL vs. 30.2 mL; p=0.09), though baseline and post-therapy left ventricular ejection fractions were comparable. Median follow-up time was 37 (IQR 13-62) months. In the IRAF cohort, 3 patients (21.4%) discontinued ibrutinib therapy, while 1 patient (7.1%) required a dose reduction. Of the 14 patients who developed IRAF, 8 were started on anticoagulation - 2 of which received full-dose therapy and 6 of which received reduced-dose therapy due to high hemorrhagic risk. One thromboembolic event occurred in the group that did not receive anticoagulation, while no such events were reported in the anticoagulated group. The incidence of hemorrhagic events was comparable between the two groups. Mortality rates were slightly higher in the IRAF group (28.6% vs. 20.3%; p=0.491), with cardiovascular-related deaths occurring in 7.1% of IRAF patients versus 1.3% without (p=0.405). Conclusion Patients who developed IRAF tended to be older, have a higher burden of cardiovascular risk factors, and larger left atrial volumes. These findings underscore the need for vigilant cardiac monitoring in high-risk patients receiving ibrutinib to optimize management strategies and minimize complications.