Analytical Validation of Patient-Specific PCR-Based MRD Assessment for Use As a Primary Endpoint in CLL Clinical Trials

Introduction. Minimal residual disease (MRD) is an objective measure of disease status defined by the number of leukemic cells in the blood or bone marrow of leukemic patients. In recent clinical studies of chronic lymphocytic leukemia (CLL), undetectable MRD levels (< 1 tumor cell/10,000 leukocytes) have been shown to correlate with prolonged progression free survival (PFS) and overall survival, independent of treatment or known risk factors. MRD assessment has been proposed as an alternative to PFS as a primary endpoint in frontline CLL pivotal studies to evaluate the efficacy of novel therapies at an earlier time-point.