BTK and B-cell chronic lymphocytic leukemia: Despite the promising efficacy of ncBTKis, a range of BTK mutations occur in patients with CLL who can develop subsequent progression on these agents, including gatekeeper mutations (T474I/F/S/L/Y), C381S/R/Y, kinase-impaired (L528W), and other mutations proximal to the ATP-binding pocket (e.g., D539A, V416L, Y545N, and A428D) [20].