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.