Measurable Residual Disease Assessment as a Surrogate Marker in New Drug Development in Acute Myeloid Leukemia

Response criteria for patients treated for acute myeloid leukemia (AML) based on cytomorphology are inadequate. Many patients achieving a complete remission by such criteria will later relapse. Patients with AML in such remissions who test negative using higher sensitivity measures of residual disease burden (measurable residual disease [MRD]) have on average lower relapse rates and better survival than those testing positive. This association has raised the possibility that these technological advances in measurement of tumor burden could be used to optimize the drug development and regulatory approval processes in AML. The heterogeneous genetic etiology, diverse immunophenotypic profiles, related precursor states and polyclonal architecture however combine to make the development of standardized and validated MRD assessments for AML challenging. Current and future methods to measure residual disease in AML, performance characteristics of testing currently in use, and potential uses for optimized AML MRD tests including as a surrogate endpoint are discussed.