'Light-chain escape-multiple myeloma'-an escape phenomenon from plateau phase: report of the largest patient series using LC-monitoring

J Cancer Res Clin Oncol. 2009 Mar;135(3):477-84. doi: 10.1007/s00432-008-0470-7. Epub 2008 Sep 18.

Abstract

Purpose: More intensive and novel therapy options in multiple myeloma (MM) hold the promise to improve treatment outcome. However, disease evolution, induced with long disease duration and extensive pretreatment, has resulted in changes in the biological behaviour of MM and unusual relapse emergence, such as of extramedullary (EM) disease or a shift in secretion from intact immunoglobulin (Ig) to free-light chains (FLCs) only.

Methods: We studied ten patients since 2004, thoroughly assessed relevant patient characteristics, prominent similarities, SFLC-changes, therapy response, mode and speed of progression, and the incidence of light-chain escape (LCE)-MM within our entire myeloma patient cohort. Serum FLCs (SFLCs) were determined via Freelite-assay (Dade-Behringer Nephelometer).

Results: This report summarizes the to date largest series of ten patients, whose MM appeared stable, as judged by conventional monitoring of intact Ig levels, but developed severe organ dysfunction as a consequence of initially undetected LC-progression. Median number of anti-MM cycles before LCE occurrence was six, including autologous and/or allogeneic stem cell transplants and novel drugs, predominantly thalidomide, in 4/10. Classic diagnostics, such as electrophoresis and quantitative Ig measurement proved futile to detect LC-progression, whereas SFLCs were reliable markers. The LCE-MM prevalence within 407 MM patients treated in our institution between 2004 and 2007 was 2.46%.

Conclusions: Our report suggests that early detection of LCE-MM by means of serial SFLC measurements may prevent unnecessary complications, allows to detect unusual relapse manifestations in the era of intensive and biological therapy options and possibly also permits to improve treatment results in LCE-MM.

MeSH terms

  • Adult
  • Aged
  • Bone Marrow / pathology
  • Female
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Immunoglobulin Light Chains / immunology*
  • Immunoglobulin kappa-Chains / immunology
  • Immunoglobulin lambda-Chains / immunology
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Neoplasm Staging

Substances

  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains