MRD as surrogate clinical trial endpoint for AML: Perspectives from MPAACT

Perspectives from a comprehensive review by the Measurable Residual Disease Partnership and Alliance in Acute Myeloid Leukemia Clinical Treatment (MPAACT) Consortium on establishing measurable residual disease (MRD) as a surrogate endpoint for clinical drug approval in acute myeloid leukemia (AML) were recently published in Cancer by Boyiadzis et al.

Overview: Multiple MRD assessment methods (flow cytometry, quantitative polymerase chain reaction [qPCR], next-generation sequencing [NGS]) demonstrate consistent prognostic value across diverse patient populations and treatment settings. MPAACT is conducting a meta-analysis across multiple randomized controlled trials to validate MRD as a surrogate endpoint for overall survival, with regulatory support from the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), and other agencies.

Key learning: MRD offers a promising pathway to accelerate AML drug development and regulatory approval, demonstrating strong individual patient-level associations with survival outcomes; formal trial-level surrogacy validation is being established through comprehensive meta-analytic approaches involving industry–academic partnerships and regulatory collaboration.