PF333 RISK OF BLEEDING COMPLICATIONS AND ATRIAL FIBRILLATION ASSOCIATED WITH IBRUTINIB TREATMENT: A SYSTEMATIC REVIEW AND META‐ANALYSIS

Abstract

Background:The use of ibrutinib is rapidly increasing because of its high potency to treat chronic lymphocytic leukaemia and other lymphoproliferative disorders. The application is however hampered by major adverse events such as bleeding complications and atrial fibrillation. The frequency and predictors of these adverse events are unknown.Aims:We aimed to study the frequency and predictors of bleeding complications and atrial fibrillation in patients treated with ibrutinib.Methods:Following a prespecified protocol, we systematically searched the literature for case series, cohort studies, as well as randomized controlled trials reporting on patients treated with ibrutinib using MEDLINE and EMBASE databases. We retrieved all relevant data in parallel. Methodological quality was observed using the Newcastle‐Ottawa Scale (NOS). Proportions of patients with bleeding events as well as atrial fibrillation were pooled in relevant subgroups using the binominal distribution and Freeman‐Tukey double arcsine transformation.Results:Among 1870 records screened, and 263 articles assessed in full‐text, 58 were finally included, comprising 4918 patients treated with ibrutinib. Methodological quality according to NOS was rated as poor to moderate. Bleeding events varied substantially with any bleedings reported between 2.8% and 78%, and major bleedings between 0% and 25% (Figure 1). New onset of atrial fibrillation was reported between 0% and 11%. Pooled estimates were 25% for any bleedings (95% confidence interval [CI] 19%, 32%); 3% for major bleedings (95% CI 2%, 4%), and 5% for atrial fibrillation (95% CI 4%, 6%). Predictors of adverse events were not apparent.Summary/Conclusion:Reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained suggests a relevant risk of bleeding events as well as atrial fibrillation in patients treated with ibrutinib.image