Evaluation of the Risk of Atrial Fibrillation/Flutter Among Patients Initiating Ibrutinib

Abstract INTRODUCTION: Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used to treat chronic lymphocytic leukemia and other hematologic malignancies. Atrial fibrillation/flutter (AF) is emerging as an adverse effect of ibrutinib therapy. The objective of this analysis was to evaluate the incidence of new AF in a real-world sample of patients initiating ibrutinib and exploring potential risk factors of AF in this population. METHODS: A retrospective cohort study of patients (age>=18) initiating ibrutinib between 01 Nov 2013 and 30 Sep 2017 was conducted using four US administrative claims databases. The databases used were MarketScan - Commercial and Medicare Supplemental Database, Optum Clinformatics Data Mart, PharmetricsPlus Adjudicated Claims Database and Humana. Patient cohorts were identified independently from each of the databases and were combined for pooled analyses after ensuring a minimum patient overlap of less than 5% among databases. The date of first prescription of ibrutinib was considered as the index date. Patients were followed from the index date to the end of index ibrutinib therapy (ibrutinib discontinuation date, follow-up end, or study end, whichever was earliest) to identify the diagnosis of new AF. Patients with an AF diagnosis prior to the index date were excluded. Baseline characteristics (including demographics, comorbidities, type of cancer and Charlson Comorbidity Index (CCI) score) were evaluated. Incident rates were calculated as number of AF events per 100 person-years and were stratified by age and gender. Cox regression models were used to estimate hazard ratios and assess potential risk factors for AF among patients receiving ibrutinib. RESULTS: The study examined outcomes in 7,276 patients treated with ibrutinib, including 4,650 (63.91%) males and 2,626 (36.09%) females, followed for a median duration of 161 days (~5.3 months). The overall incidence rate of AF was 12.5 per 100 person-years (Table 1). The median duration until AF diagnosis was 117 days (~4 months). Males were at higher risk of developing AF than females; a similar trend was observed in patients age >75 compared to younger patients. Ibrutinib patients with congestive heart failure (CHF), peripheral vascular disease (PVD) or a moderate CCI score (3-4) at baseline were at higher risk of developing AF. CONCLUSION: The incidence of AF in patients treated with ibrutinib is substantial. Older age, male gender, and baseline comorbidities (CHF and PVD) notably affect the risk of developing AF in these patients. AF should be considered when monitoring for adverse events in patients treated with ibrutinib. Disclosures Nohria: Takeda Oncology: Consultancy; Amgen: Research Funding. Rosenblatt:Bristol-Myers Squibb: Employment, Equity Ownership. Pan:Bristol-Myers Squibb: Employment, Equity Ownership. Sharma:Mu Sigma: Employment; Bristol-Myers Squibb: Consultancy.