Abstract
Over the past 3 years, ibrutinib (PCI-32765) has emerged as a breakthrough in targeted therapy for patients with certain types of B cell malignancies. Early stage clinical trials found ibrutinib to be particularly active in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), providing the rationale for ongoing phase 3 trials. In contrast to conventional chemo-immunotherapy, ibrutinib is not myelosuppressive, and responses are not affected by disease features that predict failure to respond to or short remission durations after chemo-immunotherapy, such as del17p. In CLL, ibrutinib characteristically causes an early redistribution of tissue-resident CLL cells into the blood, with rapid resolution of enlarged lymph nodes, along with a surge in lymphocytosis. Later, after weeks to months of continuous ibrutinib therapy, the growth- and survival-inhibitory activities of ibrutinib result in the normalization of lymphocyte counts and remissions in a majority of patients. This review discusses the discovery, preclinical and clinical development of ibrutinib, its pathophysiological basis, and outlines perspectives for future use of ibrutinib.
Acknowledgements
The authors are grateful to Jeannice Theriot for expert editorial assistance.
Potential conflict of interest:
Disclosure forms provided by the authors are available with the full text of this article at http://www.informahealthcare.com/lal.
This manuscript was supported by a CLL Global Research Foundation grant and a Cancer Prevention and Research Institute of Texas (CPRIT) grant (to J.A.B.).