The role of minimal residual disease measurement in multiple myeloma

Abstract: Minimal residual disease (MRD) measurement has emerged as an important tool for assessing response to treatment and predicting outcomes in patients with multiple myeloma. Traditional response criteria based on serum and urine monoclonal proteins, bone marrow plasma cells, and serum free light chain assay remain widely used, yet are insufficient to detect low levels of residual disease, necessitating more sensitive techniques. Next-generation flow cytometry (NGF) and next-generation sequencing (NGS) enable MRD detection with high sensitivity and specificity and can significantly improve prognostic stratification. The achievement of MRD negativity has consistently been associated with improved survival compared to still detectable MRD, even in patients with a complete remission status. Moreover, sustained MRD negativity, meaning sequential negative MRD tests at least one year apart, can further improve progression-free survival and overall survival. Additionally, MRD has emerged as an important endpoint for accelerated drug approval in multiple myeloma. MRD is increasingly being used to guide management, including therapy intensification or de-escalation. However, challenges such as standardization, sampling variability, false negatives in patients with extramedullary disease or patchy medullary involvement, and the need for painful bone marrow aspiration procedures still remain. This review article explores the methodologies for MRD assessment, its prognostic significance, and its evolving role in treatment optimization for multiple myeloma.