FDA Issues Draft Guidance on Use of MRD and Complete Response as End Points to Support Accelerated Approval in Multiple Myeloma
Key Clinical Summary
- Overview: On January 20, 2026, the US FDA issued a draft guidance for industry outlining recommendations for using minimal residual disease (MRD) and complete response (CR) as primary end points to support accelerated approval of drugs and biologics for multiple myeloma clinical trials.
- Key Takeaways: The guidance recognizes limitations of overall response rate (ORR) in modern myeloma trials, where ORRs now commonly exceed 60 to 70% in relapsed/refractory and ~90% in newly diagnosed disease, and proposes MRD as a more sensitive efficacy end point. It details expectations for trial design, statistical planning, and MRD assay validation, and specifies scenarios in which CR may also be acceptable for accelerated approval.
- Clinical Relevance: This guidance formalizes regulatory support for MRD-driven drug development, enabling smaller, more efficient trials and potentially faster access to effective therapies in multiple myeloma, consistent with prior ODAC consensus (April 12, 2024) endorsing MRD as an approvable end point.
On January 20, 2026, the US Food and Drug Administration (FDA) issued a draft guidance for industry with recommendations for the use of minimal residual disease (MRD) and complete response (CR) as primary end points in clinical trials evaluating drugs and biologics intended to treat patients with multiple myeloma.
This guidance, titled “Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as End Points to Support Accelerated Approval,” was issued to support accelerated approval regulations.
Accelerated approval in multiple myeloma has relied on overall response rate (ORR) supported by duration of response, enabling more rapid access to novel therapies. However, with the introduction of more effective treatments, ORRs now frequently exceed 60% to 70% in the relapsed or refractory setting and 90% in the newly diagnosed setting, making it increasingly difficult to demonstrate statistically significant differences using ORR without conducting infeasibly large clinical trials. The FDA noted that more sensitive response measures, such as MRD, may facilitate continued expeditious drug development in this disease area.
The draft guidance provides detailed recommendations on clinical trial design when proposing MRD as an end point, including general drug development considerations, trial design and statistical considerations, and assay-related considerations for MRD assessment. Additionally, the guidance also addresses circumstances in which CR may be proposed as an end point for accelerated approval, along with additional regulatory considerations.
The draft guidance builds on prior regulatory discussions, including a meeting of the Oncology Drug Advisory Committee (ODAC) held on April 12, 2024, at which the committee unanimously agreed that the use of MRD as an end point is acceptable to support accelerated approval of drugs or biologic products intended to treat multiple myeloma.
Source:
US Food and Drug Administration. Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval. Accessed January 20, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/minimal-residual-disease-and-complete-response-multiple-myeloma-use-endpoints-support-accelerated
