FDA Offers Draft Guidance on Use of MRD in Hematologic Malignancies
Posted: Friday, October 26, 2018
The U.S. Food and Drug Administration (FDA) recently released a new draft guidance to help researchers planning to use minimal residual disease (MRD) as a biomarker in clinical trials or to support marketing approval of drugs and biologics treating specific hematologic malignancies. This past April, the FDA used MRD as a biomarker for a regulatory decision for the first time.
The 18-page guidance features sections on developing MRD as a biomarker for regulatory use, including meta-analyses for validation of MRD as a surrogate endpoint, technology considerations, and disease-specific considerations. Among the hematologic malignancies featured are acute lymphoblastic leukemia, acute myeloid leukemia, acute promyelocytic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and multiple myeloma.
MRD as a measure of tumor burden has multiple potential regulatory and clinical uses as a biomarker; it “may reflect a patient’s response to treatment or may be used as a prognostic tool to assess the patient’s risk of future relapse,” the draft notes. MRD can also be used to enrich clinical trial populations or to guide allocation into specific treatment arms in trials. “The FDA views MRD as a biomarker that is a reliable quantitation of tumor burden, independent of assay,” the draft states. It also points to other potential biomarkers that researchers can use MRD status to support.
“There are challenges within each context of use that need to be addressed, such as underlying disease, patient heterogeneity, therapeutic context, target of therapy, or a combination of disease parameters, to allow effective use of MRD in regulatory decision-making,” the agency noted. Other challenges include the fact that MRD assessments can vary among laboratories and technologies, which can have different performance characteristics, according to the draft.
