Tirabrutinib hydrochloride for B-cell lymphomas.

Bruton tyrosine kinase (BTK) plays an important role in the B-cell receptor (BCR) signaling pathway by mediating proliferation, migration and adhesion in B-cell malignancies. Therefore, the components of BCR signaling, especially BTK, are considered to be attractive therapeutic targets. Ibrutinib, a first-in-class BTK inhibitor, has been approved for the treatment of several types of B-cell malignancies worldwide. However, ibrutinib has off-target activities on non-BTK kinase that are related to adverse effects or might translate into clinical limitations. To overcome these limitations, more specific BTK inhibitors are needed. Tirabrutinib hydrochloride (tirabrutinib) is a potent, highly selective, irreversible oral inhibitor of BTK. Tirabrutinib irreversibly and covalently binds to BTK in B cells and has demonstrated effective in vitro cytotoxicity in many types of B-cell malignancies and in vivo antitumor activity in mouse models. Here, we provide a comprehensive review of the preclinical and clinical activity of tirabrutinib, a drug approved in Japan for relapsed or refractory primary central nervous system lymphoma and all lines of Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. Copyright 2021 Clarivate Analytics.