Tirabrutinib (ONO/GS-4059), a highly selective irreversible BTK inhibitor, achieved a response of 35%, 92%, and 96% in relapsed or refractory ABC-DLBCL, MCL, and CLL patients, respectively, in a phase 1 trial (NCT01659255).208 M7583, a novel irreversible BTK inhibitor, is being explored in a phase 1/2 trial (NCT02825836) in patients with relapsed or refractory B-cell malignancies. This evidence concerns the gene BTK and B-cell chronic lymphocytic leukemia.