The FDA’s recent acceptance of minimal residual disease (MRD) negativity as a surrogate endpoint for accelerated approval in multiple myeloma (MM) represents a major advancement in clinical trial design and drug development. MRD negativity—defined as no detectable malignant plasma cells at a sensitivity of at least 10⁻⁵—has shown strong individual-level associations with improved progression-free and overall survival in both newly diagnosed and relapsed/refractory MM. Two major meta-analyses, EVIDENCE and I2TEAMM, provided robust data confirming that MRD-negative complete response at 9 or 12 months reliably predicts long-term outcomes. With FDA endorsement, MRD offers a more sensitive and timely endpoint than overall response rate or progression-free survival, significantly shortening trial timelines.

Unanimously supported by the FDA’s Oncologic Drugs Advisory Committee, this decision paves the way for more efficient clinical trials and faster access to new therapies—potentially reducing development timelines by years. Future trials may now combine early MRD readouts with long-term endpoints in a single study, streamlining approval pathways. The collaborative effort between industry, academia, and regulators sets a precedent for other areas in oncology to establish early surrogate endpoints. As additional trial data emerge, MRD’s role may further expand, both in MM and beyond, helping optimize drug development and accelerate patient access worldwide.

Reference: Landgren O, Devlin SM. Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap. Blood Cancer Discov. 2025;6(1):13-22. doi: 10.1158/2643-3230.BCD-24-0292.