Flow cytometry quality requirements for monitoring of minimal disease in plasma cell myeloma

Cytometry B Clin Cytom. 2016 Jan;90(1):40-6. doi: 10.1002/cyto.b.21276. Epub 2015 Sep 4.

Abstract

Current therapeutic approaches for plasma cell myeloma (PCM) attain an overall survival of more than 6 years for the majority of newly diagnosed patients. However, PFS and OS are the only accepted FDA clinical endpoints for demonstrating drug efficacy before they can be become frontline therapeutic options. There is, however, recognition that the increasing gap between drug development and approval for mainstream therapeutic use needs to be shortened. As such regulatory bodies such as the FDA are now considering whether biomarker response evaluation, as in measurement of minimal residual disease (MRD) as assessed by flow cytometry (FC), can provide an early, robust prediction of survival and therefore improve the drug approval process. Recently, FC MRD using a standardized eight-color antibody methodology has been shown to have a minimum sensitivity of 0.01% and an upper sensitivity of 0.001%. To ensure that all laboratories using this approach achieve the same levels of sensitivity it is crucially important to have standardized quality management procedures in place. This manuscript accompanies those published in this special issue and describes the minimum that is required for validating and quality monitoring of this highly specific test to ensure any laboratory, irrespective of location, will achieve the expected quality standards required.

Keywords: MRD; limit of detection; limit of quatification; minimal residual disease; multiple myeloma; plasma cells; quality assurance; quality control.

MeSH terms

  • Antigens, CD / analysis*
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Pharmacological / analysis
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Drug Approval
  • Drugs, Investigational / therapeutic use*
  • Flow Cytometry / standards*
  • Gene Expression
  • Humans
  • Immunophenotyping
  • Limit of Detection
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / mortality
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / drug therapy
  • Neoplasm, Residual / immunology
  • Neoplasm, Residual / mortality
  • Plasma Cells / drug effects
  • Plasma Cells / immunology
  • Plasma Cells / pathology
  • Prognosis
  • Quality Control
  • Remission Induction
  • Survival Analysis
  • Time Factors

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Biomarkers, Pharmacological
  • Drugs, Investigational