MRD in multiple myeloma: From an early endpoint for accelerated approval to MRD driven treatment and clinical management.

Abstract

The integration of minimal residual disease (MRD) assessment into multiple myeloma research and care has transformed the therapeutic and regulatory landscape. Building upon decades of progress in genomics, immunophenotyping, and high-sensitivity assays, MRD has now progressed from a prognostic biomarker to a U.S. Food and Drug Administration (FDA)-recognized early endpoint suitable for accelerated approval. This shift was catalyzed by the EVIDENCE meta-analysis and the I²TEAMM study, which together formed the evidentiary backbone presented at the April 2024 Oncologic Drugs Advisory Committee (ODAC) meeting. Simultaneously, prospective trials-such as PERSEUS, MIDAS, and ADVANCE-have already established the feasibility of MRD-guided treatment intensification or de-escalation. Looking ahead, the development of sensitive and reliable blood-based MRD technologies promises to expand real-time disease monitoring, streamline clinical pathways, and enable precision-based care for patients with multiple myeloma.