Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia

Progress in chronic lymphocytic leukemia (CLL) therapies has extended greatly the length and depth of remission, with the goal of treatment advancing towards a cure for some patients. Accordingly, clinical endpoints must evolve to capture these outcomes, and to provide faster access to novel therapies. Minimal residual disease (MRD) is an important endpoint representing more accurately the depth of remission than complete response (CR), and is highly prognostic of progression-free survival (PFS) and overall survival (OS). MRD could be considered a key outcome of clinical trials and, as a surrogate for PFS, could identify the most cost-effective and durable treatment sequencing. MRD testing could also determine which patients would benefit from additional therapy and, accordingly, ascertain when therapy should be stopped earlier, to reduce toxicity and increase treatment-free intervals. Our article discusses possible uses of MRD in the modern era of CLL, including its definition, measurement, and value as a surrogate endpoint in clinical trials, and its potential roles in clinical practice.