Chemoimmunotherapy of chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) has long been regarded as an incurable disease of the elderly, worthy only of symptom palliation. Past generations of chemotherapy resulted in improved response rates, but did not change the natural history of the disease. Prolonged remissions and improvements in survival are, however, now possible owing to therapeutic advances including the use of purine analogs as frontline treatment and the emergence of monoclonal antibody-containing chemoimmunotherapy combinations. Moreover, consolidation strategies using non-cross resistant agents have improved the success rates of patients with residual disease at the end of induction treatment. Together, these new developments promise to deliver the tools necessary to render a state of minimal residual disease negativity in the majority of patients commencing treatment for CLL. This Review will outline the history and results of chemoimmunotherapy regimens that contain purine analogs and rituximab-the most successful combinations developed to date. We will also discuss how new developments in induction and consolidation strategies are leading the path towards cure.