FDA issues Draft Guidance for Industry on using MRD and CR as Primary Endpoints in Multiple Myeloma Drug Trials to support Accelerated Approval

On January 20, 2026, the Food and Drug Administration issued a draft guidance for industry that provides recommendations to sponsors about using minimal residual disease (MRD) and complete response (CR) as primary endpoints in trials evaluating drugs and biologics intended to treat patients with multiple myeloma to support approval under the accelerated approval regulations. 

The draft guidance, “Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval,” provides specific recommendations for designing clinical trials using MRD as an endpoint for accelerated approval. These recommendations include general drug development considerations, trial design and statistical considerations, and assay considerations for MRD evaluation. The guidance also includes considerations when proposing CR as an endpoint for accelerated approval as well as other regulatory considerations.

In multiple myeloma, accelerated approval based on an endpoint of overall response rate (ORR) supported by duration of response has expedited the approval of new therapies. However, the ORRs observed with new therapies have surpassed 60-70% in the relapsed or refractory setting and 90% in the newly diagnosed setting. With the improved outcomes observed in this disease area demonstrating statistically significant differences in ORRs may require infeasibly large clinical trials. Additionally, more sensitive response assessments will allow for continued expeditious drug development. 

On April 12, 2024, Oncology Drug Advisory Committee unanimously agreed that it is acceptable to use MRD as an endpoint to support accelerated approval of drugs or biologic products intended to treat multiple myeloma.