title: Regulatory perspective on minimal residual disease flow cytometry testing in multiple myeloma.
abstract: The FDA has co-sponsored three workshops to address minimal residual disease (MRD) detection in acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and acute myeloid leukemia (AML) as well as an FDA-NCI roundtable symposium on MRD detection and its use as a response biomarker in Multiple Myeloma (MM). As clinical outcomes in MM continue to improve with the introduction of new therapeutics, consideration of biomarkers and their development as validated surrogate endpoints that can be used in the place of traditional clinical trial endpoints of progression-free survival (PFS) will be fundamental to expeditious drug development. This article will describe the FDA drug approval process, the regulatory framework through which a biomarker can be used as a surrogate endpoint for drug approval, and how MRD detection in MM fits within this context. In parallel, this article will also describe the FDA current device clearance process with emphasis on the analytical development as it might apply to an in vitro diagnostic assay for the detection of MRD in MM. It is anticipated that this Special Issue may possibly represent how MRD might serve as a drug development tool in hematological malignancies.
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Gormley
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Turley
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Dickey
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Ann T
authors.initials: AT
authors.lastname: Farrell
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stafford
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Lea
authors.initials: L
authors.lastname: Carrington
authors.affiliation: Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiologic Health (CDRH), Food and Drug Administration (FDA).
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Marti
mesh_terms: D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000032:analysis; D018795:Device Approval / Q000331:legislation & jurisprudence; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D005434:Flow Cytometry / Q000592:standards*; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological
keywords: B cells; FDA; MM; MRD; flow cytometry; hematology