The Food and Drug Administration (FDA) approval of the first covalent BTK inhibitor (cBTKi), ibrutinib, for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenström’s macroglobulinemia (WM) marked the beginning of a chemotherapy-free era in the management of B-cell malignancies [5–7]. The gene discussed is BTK; the disease is B-cell chronic lymphocytic leukemia.