Novel targeted treatment strategies for refractory chronic lymphocytic leukaemia

Patients with refractory chronic lymphocytic leukaemia (CLL) still have an unfavourable prognosis and novel treatment strategies are necessary, preferably adjusted to the patient's individual situation. Refractoriness is no longer limited just to fludarabine (F) but extends to F-combinations with other chemotherapeutic agents (e.g. cyclophosphamide [C] and FC) and antibodies (e.g. rituximab [R], FR, and FCR). Also, refractoriness to alemtuzumab is an increasing problem. New pharmacological developments provide promising approaches. This review focuses on novel therapies such as monoclonal antibodies and small molecules aiming at specific targets of the CLL cell in the refractory situation. Approved therapeutic regimens will be presented as well as investigational approaches. An overview of completed and current clinical trials is offered.