Voyage of Measurable Residual Disease (MRD) Assessment in Multiple Myeloma Using Multiparametric Flow Cytometry

Abstract Measurable residual disease (MRD) in multiple myeloma (MM) has emerged as one of the strongest and independent biomarkers to evaluate therapeutic response for the prediction of long-term treatment outcome. With the incorporation of MRD in response assessment criterion by International Myeloma Working Group, it has become the routine parameter to be assessed at various time points after therapy. Among various techniques to assess MRD, multiparametric flow cytometry (MFC)-based MRD estimation has evolved dramatically over the last two decades achieving sensitivity comparable to molecular methods. Next-generation flow cytometry with the incorporation of innovative tools in MRD detection including consortium-based guidelines for preanalytical and analytical factors led to the overall improvement in MFC-based MRD detection. However, flow cytometry assays suffer from inherent challenges ranging from procedural hemodilution to lack of harmonization and standardization across the centers. This review article outlines and summarizes the essential laboratory prerequisites for reproducible MRD analysis by flow cytometry. Furthermore, a brief account of the utility of MRD evaluation in clinical practice as predictor of response and long-term treatment outcome has also been discussed. Considering the evolution of MFC-based MRD over two decades from a scientific research tool to a routine clinical diagnostic assay, it needs to be explored further in studying complex phenomenon like clonal evolution, clonal switches, and identification of treatment refractory clones for guiding more effective therapies improving overall survival.