Minimal residual disease (MRD) is an important prognostic marker in mature B-cell and plasma cell malignancies, providing sensitive assessment of treatment response and risk of relapse. Next-generation sequencing (NGS) enables highly sensitive detection of MRD through identification and tracking of immunoglobulin gene rearrangements associated with malignant clones of B-cell origin. This review outlines the principles of NGS-based MRD assessment and its application in mature B-cell and plasma cell malignancies including several mature B-cell lymphomas, chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). The advantages of NGS, such as high sensitivity and ability to use a range of sample types, are discussed alongside its limitations, including the requirement for baseline diagnostic samples and cost. Current evidence suggests that NGS is a powerful tool for MRD detection and is increasingly being incorporated into clinical trials as a response endpoint, with potential to guide treatment strategies such as escalation of therapy in routine clinical practice.
McAvera et al. (2026) studied this question.