Using MRD Data to Expedite Myeloma Treatment Delivery: Nicholas Richardson, DO, MPH

In January, the FDA released draft guidance proposing the use of minimal residual disease (MRD) and complete response as primary end points to support the accelerated approval of drugs for multiple myeloma (MM).¹ This shift is intended to expedite the delivery of new therapies, as modern treatments have significantly improved patient survival rates.

Under this framework, MRD negativity is defined as having less than 1 myeloma cell per 1 million bone marrow cells, typically assessed via flow cytometry or sequencing following a complete response (CR). A CR is considered achieved when monoclonal protein (M-protein) is undetectable in the blood. Although MRD is a strong prognostic factor in MM, Nicholas Richardson, DO, MPH, clarifies that it is categorized as an intermediate clinical end point—meaning it is reasonably likely to predict clinical benefit—rather than a "true surrogate end point," which must meet more rigorous scientific criteria. He is vice president of clinical development at Precision for Medicine and former FDA deputy director for the Division of Hematologic Malignancies.

Consequently, the guidance focuses specifically on regulatory decision-making for accelerated approval rather than guiding individual clinical treatment decisions or usage in the maintenance setting, which Richardson explains requires further analysis.

The guidance, developed through a collaboration between the Oncology Center of Excellence, Center for Drug Evaluation and Research, Center for Biologics Evaluation and Research, and Center for Devices and Radiological Health, outlines strict requirements for trial design. Randomized trials are preferred over single-arm studies because they allow for the continued investigation of progression-free survival and overall survival as secondary or safety end points.

Furthermore, the FDA provides specific instructions for drug development, including the need for robust data collection; the use of predefined statistical analyses; methods to minimize bias, such as standardized bone marrow aspirate assessments; and complete trial enrollment before the targeted end point is analyzed for approval. Although these recommendations are not currently legally binding, they reflect the agency's evolving thinking on quantifying treatment depth. Public comments on the draft are being accepted through March 23, 2026

Reference

Shaw ML. FDA draft guidance proposes CR, MRD to accelerate MM drug approval. AJMC^®. January 21, 2026. Accessed February 12, 2026. https://www.ajmc.com/view/fda-draft-guidance-proposes-cr-mrd-to-accelerate-mm-drug-approval