Molecular End Points Poised to Transform Myeloma Drug Approval: Nicholas Richardson, DO, MPH

In January, the FDA released draft guidance proposing minimal residual disease (MRD) negativity and complete response as primary end points to support accelerated approval of drugs for multiple myeloma, a move intended to speed access to therapies that have already meaningfully extended patient survival. At that time, The American Journal of Managed Care^® spoke to Nicholas Richardson, DO, MPH, vice president of clinical development at Precision for Medicine and former FDA deputy director for the Division of Hematologic Malignancies, about the proposed guidance. He offered clarification about the use of MRD and MRD-negative status as FDA end points for faster multiple myeloma approval.

Under the framework, MRD negativity is defined as fewer than 1 myeloma cell per 1 million bone marrow cells, assessed by flow cytometry or sequencing following a complete response. Richardson explained that MRD functions as an intermediate clinical end point—reasonably likely to predict clinical benefit—rather than a validated surrogate, which carries a higher evidentiary bar. Accordingly, the guidance is scoped narrowly to regulatory decision-making for accelerated approval and does not address individual treatment decisions or maintenance settings.

In this second part of that interview, Richardson explains that he sees MRD as a natural evolution of oncology’s existing regulatory toolkit. Because tumors do not shrink without intervention, response rate has long served as a reliable early signal of drug activity in multiple myeloma, supporting a decade of accelerated approvals and steady survival gains. MRD assessment adds molecular-level resolution to that picture.

“MRD is really well-positioned in multiple myeloma to support an early assessment of activity, leverage the accelerated approval program, and really afford access to new and novel therapies for patients with multiple myeloma,” Richardson said.

The guidance, developed collaboratively across 4 FDA centers, sets rigorous trial design expectations: Randomized studies are preferred over single-arm designs and requirements include robust data collection, predefined statistical analyses, standardized bone marrow aspirate assessments to minimize bias, and full enrollment prior to end point analysis. Although not yet legally binding, the recommendations signal the agency's direction.

Public comment was open through March 23, 2026.