Ibrutinib as a Bruton Kinase Inhibitor in the Management of Chronic Lymphocytic Leukemia: A New Agent With Great Promise

The recent discovery of the role of the B-cell antigen receptor (BCR) signaling pathway in the propagation and maintenance of both normal B-cell function and in B-cell malignancies has highlighted the importance of many protein kinases involved in BCR signal propagation. Considerable research attention has focused on the Bruton tyrosine kinase (BTK) as a potential therapeutic target in B-cell malignancies. Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia. This has provided additional treatment options, especially among the elderly, where improved disease response has been accompanied by more manageable treatment-associated toxicity than commonly found with chemoimmunotherapy. In this review, we provide a synopsis of the current data on the efficacy and clinical utilization of ibrutinib and management of its resistance in the treatment of chronic lymphocytic leukemia.