Chronic lymphocytic leukemia (CLL), a cancer of B-cell lymphocytes, is the most common type of leukemia in adults. Ibrutinib is a potent, small molecule inhibitor of BTK that has revolutionized the treatment approach of CLL patients. A major cause of morbidity in patients treated with ibrutinib is atrial fibrillation that represents a high risk for cardioembolic stroke and systemic embolism. Treatment and prevention of cardioembolic stroke and systemic embolism of atrial fibrillation pose a clinical challenge in balancing thrombosis and bleeding risks in patients taking ibrutinib, a drug that is associated with an anti-aggregant effect. Very limited data and conflicting opinions are available about the use of direct-acting oral anticoagulants (DOACS) or other anticoagulants/antiaggregant agents in the ibrutinib-treated population. At present, recommendations about the use or not of DOACS are not supported by studies including representative cohorts of patients treated with these agents. The primary endpoints of this multicenter, observational, retrospective/prospective study are to define the rate of thromboembolic events and severe bleeding events in CLL patients who develop atrial fibrillation while on ibrutinib and receive anticoagulation with DOACS or other anticoagulants/ antiaggregant treatment. Secondary endpoints will describe the clinical and biologic characteristics of CLL patients requiring anticoagulation due to atrial fibrillation, the type of DOACS (Rivaroxaban, Apixaban, Edoxaban, Dabigatran) or other anticoagulants/antiaggregant treatment (Low-molecular-weight heparin, aspirin, clopidogrel, etc) used in this patient population. We will also analyze the reasons for anticoagulant discontinuation, the management of anticoagulant treatment, and the survival probability of CLL patients treated with anticoagulants and ibrutinib.
