Chronic lymphocytic leukemia: what clinical progress have we seen in the last five years?

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults. Although treatment has shifted from immunochemotherapy to novel targeted drugs over the last ten years, novel therapies remain under investigation, particularly in relapsed and refractory patients. This review describes the use of approved targeted drugs and novel therapies in treatment-naïve and relapsed or refractory CLL. Particular attention is paid to the management of double-refractory patients, and the discovery of novel drugs in the last five years. Targeted drugs are effective and well-tolerated in the treatment of CLL. In the last five years, several novel agents have been investigated in preclinical studies and clinical trials, including combinations of approved drugs, novel BTK and BCL2 inhibitors, BTK degraders, bispecific antibodies and CAR-T cells. It is anticipated that some should be approved in the near future.