RESUMEN
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.
Asunto(s)
Antígenos CD/análisis , Antineoplásicos/uso terapéutico , Aprobación de Drogas/legislación & jurisprudencia , Citometría de Flujo/normas , Mieloma Múltiple/diagnóstico , Neoplasia Residual/diagnóstico , Antígenos CD/genética , Antígenos CD/inmunología , Biomarcadores Farmacológicos/análisis , Aprobación de Recursos/legislación & jurisprudencia , Expresión Génica , Humanos , Inmunofenotipificación , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Mieloma Múltiple/mortalidad , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/inmunología , Neoplasia Residual/mortalidad , Células Plasmáticas/efectos de los fármacos , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Pronóstico , Inducción de Remisión , Análisis de Supervivencia , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Recent advances in cancer therapy are based on agents that specifically target the products of the genes mutated in cancer cells. Development of companion diagnostic tests for these agents can simplify the drug-discovery process, make clinical trials more efficient and informative, and be used to individualize the therapy of cancer patients. Companion diagnostic development has many challenges. Examples include the reluctance of drug companies to restrict the use of their drugs through biomarker tests, difficulties of developing companion diagnostics from discovery to clinical validation, and the regulatory challenges in developing effective mechanisms to synchronize reviews of therapeutics with diagnostic devices used to personalize treatment. This article addresses the various challenges in developing companion diagnostics along with the US FDA's approach to regulation of companion diagnostic devices.