Clinical trials in early-stage CLL: what has been learned and what's next?

More than 80% of newly diagnosed chronic lymphocytic leukemia (CLL) patients present with asymptomatic, early-stage CLL. Of these, only 30-50% progress to advanced stage with reduced survival, while the rest may never require treatment. According to the 2018 International Workshop on CLL (iwCLL) guidelines, patients who do not meet the criteria for treatment initiation should only be treated within the context of clinical trials, as data demonstrating an overall survival benefit in early-stage CLL are still awaited. Risk stratification through continually advancing prognostic models can assist in identifying high-risk patients for early, risk-adapted treatment within clinical trials. Currently, new targeted therapies with high efficacy and lower toxicity are available in early intervention trials. This review (1) explores the development of prognostic models for identifying high-risk patients, (2) examines the design of early intervention trial, (3) summarizes the outcomes of early intervention trials, particularly in the context of targeted therapies, and (4) highlights ongoing clinical trials involving targeted treatments.