Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

Minimal residual disease (MRD) is considered the strongest relevant predictor of prognosis and an effective decision-making factor during the treatment of hematological malignancies. Remarkable breakthroughs brought about by new strategies, such as epigenetic therapy and chimeric antigen receptor-T (CAR-T) therapy, have led to considerably deeper responses in patients than ever, which presents difficulties with the widely applied gold-standard techniques of MRD monitoring. Urgent demands for novel approaches that are ultrasensitive and provide sufficient information have put a spotlight on high-throughput technologies. Recently, advances in methodology, represented by next-generation sequencing (NGS)-based clonality assays, have proven robust and suggestive in numerous high-quality studies and have been recommended by some international expert groups as disease-monitoring modalities. This review demonstrates the applicability of NGS-based clonality assessment for MRD monitoring of B-cell malignancies by summarizing the oncogenesis of neoplasms and the corresponding status of immunoglobulin (IG) rearrangements. Furthermore, we focused on the performance of NGS-based assays compared with conventional approaches and the interpretation of results, revealing directions for improvement and prospects in clinical practice.

Automated summary

Minimal residual disease (MRD) is the strongest predictor of prognosis and a crucial factor in treatment decisions for hematological malignancies. Advances in new strategies have resulted in deeper responses in patients, making it challenging for the widely used gold-standard techniques of MRD monitoring. High-throughput technologies, such as next-generation sequencing (NGS)-based clonality assays, are recommended as disease-monitoring modalities due to their sensitivity and ability to provide sufficient information.