BTK and B-cell chronic lymphocytic leukemia: However, over the last 20 years, the treatment of either naïve or relapsed/refractory CLL patients has undergone dramatic changes due to the introduction of targeted therapeutics which include the Bruton tyrosine kinase (BTK) inhibitor ibrutinib [119] and the Bcl-2 inhibitor venotoclax [120], and the PI3K inhibitors idelalisib [121] and duvelisib [73].