Minimal residual disease analysis in chronic lymphocytic leukemia: a way for achieving more personalized treatments

Therapeutic approaches for chronic lymphocytic leukemia (CLL) have dramatically changed over the recent past. In parallel, quantification of minimal residual disease (MRD) proved to be an independent prognostic factor for progression-free and overall survival. The European Research Initiative on CLL (ERIC) in collaboration with American and Australasian partners developed harmonised assays that could be applied reproducibly to compare the efficacy of different treatments. The potential for MRD analysis to identify the most effective treatments prior to reaching survival endpoints was recognised by regulatory agencies and approved as an intermediate endpoint for licensure in randomized studies, in Europe. More recently treatment approaches have evolved, in particular with BCL2-pathway inhibitors, so that MRD analysis may be informative for most patients and clinical trials, potentially becoming a tool for managing CLL patients in clinical practice. In the recent past the importance of the type of MRD assay used, the most appropriate timing and compartment to assess for different treatment types have been learnt as we move towards eradicating residual disease beyond the guideline threshold of one cell in ten thousand. Nowadays, MRD assessment in CLL has quickly become an indispensable tool for clinical research and development that promise to change the way we manage our patients in the future.