Approaches to the prevention and therapy of ibrutinib-associated bleeding in adult patients

Abstract

Ibrutinib, an irreversible Bruton tyrosine kinase inhibitor (Btk), is a highly effective drug for treatment a number of B-cell lymphoproliferative disorders and, more recently, graft-versus-host disease. However, a number of potentially adverse events are possible in this therapy, partly related to the non-selective mechanism of the drug’s action. Thus, ibrutinib therapy significantly increases the risks of hemorrhagiccomplications compared to standard chemotherapy, especially when combined with a disagregant or anticoagulant therapy, which necessitates the development of clinical recommendations taking into account individual risks for the prevention and treatment of bleeding complications in patients receiving ibrutinib. There is currently an amount of data on the combined use of ibrutinib with disaggregant or anticoagulant therapy is limited, and it is therefore recommended that alternative therapy be considered in patients with a high cardiovascular risk ora reduction in the doses of disaggregante or anticoagulant drugs if abrogation or alternative therapy with ibrutinib is not possible. Also takinginto account the antiplatelet effects of a non-selective Btk inhibitor, a modification of the disaggregant therapy in patients with low cardiovascular risk is possible. This review is summarized available data on mechanisms of bleeding development and proposed strategies for reducingrisks and treating hemorrhagic complications of therapy with ibrutinib.