Best practices for the assessment of measurable residual disease (MRD) in multiple myeloma

Therapeutic advances in multiple myeloma have led to durable, deep remissions in a subset of patients. However, outcomes of patients achieving a complete response are not homogeneous. In recent years, measurable residual disease (MRD) has emerged as a prognostic biomarker. While several technologies have been evaluated to detect MRD, two assessment technologies are most frequently utilized in patients with multiple myeloma. Next-generation flow (NGF) uses flow cytometry to identify malignant plasma cells through the presence of immunologic markers located on the cell surface. Next-generation sequencing (NGS) analyzes for the presence of sequences in immunoglobulin genes that were previously identified as markers of that specific patient's plasma cell malignant clone. Both methods are included in criteria for MRD by the International Myeloma Working Group, which defines MRD negativity as less than 10^-5. Recently, the NGS-based clonoSEQ® Assay obtained clearance from the US Food and Drug Administration, with a limit of detection of less than 10^-6 given proper sample input. Based on available evidence correlating attainment of MRD negativity with outcomes, MRD assessment has been incorporated into ongoing clinical trials. Analyses will provide additional insight into the correlation between MRD and outcome. This monograph examines the available trial data and provides recommendations on how to incorporate MRD assessment into clinical management.