Evidence Supporting MRD Negativity as a Prognostic and Regulatory Endpoint in Multiple Myeloma

In this segment, Dr. Joseph Mikhael asks Dr. Scott Goldsmith to explain the evidence supporting the use of minimal residual disease (MRD) negativity as an endpoint for regulatory decision-making in multiple myeloma. Dr. Goldsmith reviews evidence accumulated over the past 10 to 15 years demonstrating associations between MRD negativity and clinically meaningful outcomes, including progression-free survival (PFS) and overall survival (OS). He explains the biological rationale that deeper treatment responses may be associated with longer remissions and improved survival. Dr. Goldsmith also discusses how the FDA and its Oncologic Drugs Advisory Committee (ODAC) conducted pooled analyses of pivotal clinical trials to independently evaluate the relationship between MRD negativity and these outcomes. As contemporary therapies achieve increasingly high conventional response rates, he highlights the potential value of MRD negativity as an earlier biomarker for assessing deep responses and supporting accelerated approval. He emphasizes the importance of prospectively establishing that MRD negativity correlates with meaningful clinical outcomes.