Abstract Body (Do not enter title and authors here): Introduction
Bruton’s tyrosine kinase inhibitors (BTKi) have significantly advanced treatment of mantle cell lymphoma (MCL). This study evaluates the incidence and risk factors for cardiovascular adverse events (CVAEs) in MCL patients receiving BTKi, correlating CVAEs with risk stratification by the European Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS).

Methods
In this retrospective study, demographic and clinical variables, and CVAEs were extracted from clinical records of MCL patients treated with BTKi. Patients were stratified into low, medium, high, and very high-risk groups using the HFA/ICOS tool. Exposure time, from BTKi initiation to 90 days post-treatment, was expressed per 100 person-years. The incidence rate (IR) of CVAEs included palpitations, arrhythmias, blood pressure medication initiation, heart failure, coronary artery disease, stroke, CVAE-related hospitalizations, bleeding, and death. Cox regression models analyzed the association of clinical and demographic characteristics with CVAEs.

Results
We included 298 patients (85% untreated, 15% relapsed MCL), median age 65.6 years (IQR 57.6-71.5), predominantly White males (92%, 79%). Comorbidities at BTKi initiation included hypertension (44%), hyperlipidemia (37%), diabetes (11%), and history of atrial fibrillation (AF, 8%), with 2% having AF at therapy initiation. Median left ventricular ejection fraction was 60% (IQR 57-63) and the left atrial volume index 24.6 ml/m² (IQR 19.0-30.3). Ibrutinib was used in 60% and second-generation BTKis in 40%. Over a median BTKi exposure of 1 year (range 0.06-8.34), 99 subjects experienced AEs with an IR of 20.8 per 100 person-years. HFA/ICOS low-risk patients had the lowest IR (16.7/100 person-years, 95% CI 6.1-32.5), and the very high-risk group the highest IR (31.9/100 person-years, 95% CI 19.2-47.8). Seventeen patients (5.7%) developed new-onset AF, 7.2% on Ibrutinib and 4.3% on second-generation BTKi. Independent predictors of CVAEs included a history of AF (HR 1.80, 95% CI 1.01-3.22; p=0.047) and prior BTKi exposure within 90 days (HR 3.67, 95% CI 1.77-7.59; p<0.001).

Conclusions
Patients with a history of AF were at higher risk for CVAEs when treated with BTKi for MCL. The HFA/ICOS risk tool identified MCL patients at the highest risk for CVAEs with BTKi, highlighting the need for tailored monitoring strategies to optimize patient care and resource utilization.