BTK and B-cell chronic lymphocytic leukemia: The first-generation inhibitor of Btk (iBtk), ibrutinib, is an effective therapeutic strategy for CLL but has significant toxicity, particularly related to infections and hemorrhagic complications (5–8), due to inhibition of Btk expressed in other (non-B lymphocyte) hematopoietic cells and off-target effects on other kinases (9–11).