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Abstract
Introduction: Chemoimmunotherapy has improved response rates and overall survival (OS) in patients with chronic lymphocytic leukemia (CLL). Despite these advances, CLL remains an incurable disease outside of stem cell transplantation. B-cell receptor (BCR) signaling is a pivotal pathway in the pathogenesis of CLL by promoting survival and proliferation of CLL cells. Bruton's tyrosine kinase (BTK) is essential for BCR signaling and can be irreversibly inhibited by ibrutinib (PCI 32765).
Areas covered: The clinical presentation and current treatment of CLL are briefly reviewed before focusing on the role of BCR signaling in the pathogenesis of CLL. The development of ibrutinib and the preclinical and clinical experience with this targeted agent in CLL are discussed.
Expert opinion: Ibrutinib and other kinase inhibitors targeting BCR signaling are heralding a new era in the treatment of CLL. Efficacy and tolerability of ibrutinib are equally impressive and make it the most active monotherapy in CLL. Ibrutinib does not appear to increase the risk of infections, and the development of drug resistance is uncommon, providing a foundation for possible long-term therapy with this agent. Treatment goals and strategies will become more evident as we learn more about duration of response, mechanisms of resistance, tolerability of chronic use, and results with combination therapies.