Inhibition of the Bruton Tyrosine Kinase Pathway in B-Cell Lymphoproliferative Disorders

Activation of the Bruton tyrosine kinase (BTK) pathway plays an important role in the pathophysiology of a number of B-cell lymphoproliferative disorders (LPDs). A number of preclinical studies support inhibiting BTK as a mechanism to treat LPDs. Clinically, BTK inhibitors, specifically ibrutinib, have shown to be safe and effective on treating patients with indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). Ibrutinib has recently gained approval for the treatment of patients with mantle cell lymphoma, Waldenström macroglobulinemia, and CLL. Ongoing clinical trials are investigating ibrutinib and other BTK inhibitors alone or in combination for the treatment of mantle cell lymphoma, Waldenström macroglobulinemia, CLL, activated B-cell-type diffuse large B-cell lymphoma, and follicular lymphoma, among others. The objective of this review is to succinctly summarize the current body of evidence on BTK inhibition in patients with B-cell LPDs.