Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap
Ola Landgren, Sean M. Devlin
Abstract
Abstract Improvements in multiple myeloma treatments have extended patient survival to a decade or more. Treatment response rates >90% have introduced new challenges for drug development, including a need for early endpoints with greater sensitivity. The FDA, based on data from two independent academic research groups and industry, evaluated minimal residual disease (MRD) negativity as an intermediate endpoint for progression-free and overall survival, culminating in a unanimous vote by the Oncologic Drugs Advisory Committee in April 2024 supporting MRD-negative complete response as an early endpoint reasonably likely to predict clinical benefit in multiple myeloma that may be used to support accelerated approval. Significance: The acceptance of MRD-negative complete response as an endpoint that is reasonably likely to predict clinical benefit will allow for the design of streamlined clinical trials for accelerated approval, enabling significantly faster patient access to novel therapies. Cooperative efforts were required to obtain and analyze clinical trial data from multiple sponsors and to determine the best approach to analysis with a relatively limited number of available datasets. The process to evaluate MRD as an intermediate endpoint, undertaken jointly by myeloma researchers and industry, with feedback from the FDA, serves as a roadmap for other areas of oncology to develop intermediate endpoints.