Excerpt

Plasma cell dyscrasias (PCDs) are a group of clonal disorders characterized by the uninhibited expansion of a monoclonal population of malignant plasma cells. Plasma cells arise from B cells in the bone marrow and produce immunoglobulins that constitute the body’s normal humoral immune response. The immunoglobulin molecule is composed of a heavy chain and a light chain. Plasma cells normally produce light chains in excess that do not bind to heavy chains to form a complete immunoglobulin molecule and instead enter the bloodstream as free light chains (FLCs). In PCDs, each abnormally expanded clone of malignant plasma cells produce an excess of either intact immunoglobulin or FLCs of a single type called a monoclonal protein (M-protein) or paraprotein.

The serum FLC (SFLC assay (the Freelite™ Assay, The Binding Site Ltd., Birmingham, United Kingdom) was introduced in 2001 to measure the FLC component in particular. The SFLC assay works by recognizing an epitope that is detectable only on light chains that are not bound to the heavy chain of the immunoglobulin molecule (i.e., FLCs) in the serum. This is the sole SFLC assay approved by the U.S. Food and Drug Administration. It detects low concentrations of FLCs and can measure the ratio of kappa chains to lambda chains.

It has been suggested that the SFLC assay could play an adjunctive role in screening, diagnosis, monitoring, and prognosis of PCDs in high-risk populations. The International Myeloma Working Group (IMWG) currently considers the SFLC assay to be an adjunct to traditional tests. The assay could allow for quantitative monitoring of response and remission after treatment and provide prognostic information, potentially reducing the need for frequent bone marrow biopsy for purposes of quantifying plasma cells, which is required as part of stringent monitoring for monoclonal gammopathy of undetermined significance (MGUS) progression to multiple myeloma (MM) or defining disease remission, and potentially could be used in conjunction with serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) to replace urine tests that require 24-hour collection (urine protein electrophoresis [UPEP] and urine immunofixation electrophoresis [UIFE]), which could simplify diagnosis and disease monitoring. The SFLC assay may also be the only means of detecting a disease marker in some disease settings: nonsecretory MM, where SFLCs are often the only marker of the disease; AL amyloidosis (systemic amyloidosis in which amyloid [A] proteins derived from immunoglobulin light chains [L] are deposited in tissue), where low monoclonal protein (M-protein) concentrations may not be detected by means of conventional techniques; and light chain MM, where the M-protein consists only of FLCs. These diagnostic applications have yet to be validated and standardized. Thus, although the SFLC assay has been in use for a decade, it remains unclear how best to incorporate it into clinical practice.

Contents

• Preface
• Acknowledgments
• Contributors
• Executive Summary
• Background
  • Scope of the CER
  • Evidence Gaps
• Methods
  • Identification of Evidence Gaps
  • Criteria for Prioritization
  • Engagement of Stakeholders, Researchers, and Funders
  • Research Question Development and Research Design Considerations
• Results
  • Research Needs
• Discussion
• Conclusions
• References
• Abbreviations
• Appendix A Search Strategy for Ongoing Studies
• Appendix B Lists of Ongoing Studies

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services¹, Contract No. 290-2007-10055-I, Prepared by: Tufts Evidence-based Practice Center, Tufts Medical Center, Boston, MA

Suggested citation:

Rao M, Lamont JL, Chan J, Concannon TW, Comenzo R, Ratichek SJ, Avendano EE. Serum Free Light Chain Analysis for the Diagnosis, Management, and Prognosis of Plasma Cell Dyscrasias: Future Research Needs. Future Research Needs Paper No. 23. (Prepared by Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-I.) AHRQ Publication No. 12-EHC135-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2012. www.effectivehealthcare.ahrq.gov/reports/final.cfm.

This report is based on research conducted by the Tufts Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2007-10055-I). The findings and conclusions in this document are those of the author(s), who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care researchers and funders of research make well-informed decisions in designing and funding research and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of scientific judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical research and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances.

None of the investigators have any affiliation or financial involvement that conflicts with the material presented in this report.

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