Role of minimal residual disease assessment in multiple myeloma

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized by clonal proliferation of plasma cells. MM is a heterogeneous disease, featured by various molecular subtypes with different outcomes. With the advent of very efficient therapies including monoclonal antibodies, bispecific T cell engagers and chimeric antigen receptor T cells (CAR T cells), most of MM patients have now a prolonged survival. However, the disease remains incurable, and a subgroup of high-risk patients continue to have early relapse and short survival. Novel and highly sensitive methods have been developed allowing to detect minimal residual disease (MRD) during or after treatment. Achievement of MRD negativity is a strong and independent prognosis factor in both prospective randomized clinical trials and in real-world setting. While MRD assessment is now a validated endpoint in clinical trials, its incorporation in clinical practice is not yet established and its potential impact on guiding therapy remains under deep evaluation. We discuss in this chapter, the different available methods allowing MRD assessment and the role of MRD evaluation in multiple myeloma management.

The Challenging Approach to Multiple Myeloma: From Disease Diagnosis and Monitoring to Complications Management

“…NGF, using 2-tube 8-color methodology [ 53 ] or single-tube 10- or 12-color methodology [ 54 ], achieves a sensibility between 10-5 and 10-6 and does not require a sample at diagnosis [ 55 ]. In contrast, NGS, able to reach a sensitivity of 10-6, requires a baseline bone marrow sample to identify the predominant clone that can be detected in almost 90% of MM patients [ 56 ]. In a prospective MRD analysis of the Phase II FORTE trial [ 57 ], enrolled transplant eligible NDMM, NGF and NGS were concordant in 87% and 83% analyses at the 10-5 and 10-6 cut-off, respectively, translating into a clinical and prognostic concordance, being HRs in NGF-MRD and NGS-MRD negative vs. positive patients of 0.29 and 0.27 for PFS and 0.35 and 0.31 for OS, respectively ( p < 0.05).…”