Evaluation of the serum free light chain (sFLC) analysis in prediction of response in symptomatic multiple myeloma patients: rapid profound reduction in involved FLC predicts achievement of VGPR

Eur J Haematol. 2014 Nov;93(5):407-13. doi: 10.1111/ejh.12376. Epub 2014 Jun 14.

Abstract

Background: Observational data from clinical studies indicate that the goal of first-line therapy in newly diagnosed patients with symptomatic multiple myeloma (MM) should be very good partial response (VGPR) or better, preferably before high-dose treatment. We evaluated the value of early measurements of involved free light chains (iFLC) in prediction of high-quality responses. Measuring iFLC has a potential advantage due to a short half-life compared to the half-life of the M-protein.

Methods: In 36 multiple myeloma (MM) patients, we measured serial changes in iFLC and M-protein after start of treatment. iFLC and M-protein were measured before treatment, the following 5 wk days, 2, 3 and 6 wks after start of treatment.

Results: Median iFLC and M-protein half-life was 2.75 and 11.9 d, respectively. All patients with an iFLC >75 mg/L had an initial significant reduction (>20%) in iFLC, even patients with no response to treatment. The mean per cent reduction in iFLC 3 d after start of treatment was 52.3% and 23.6% (P = 0.021) in patients achieving ≥VGPR and PR, respectively. The mean per cent reduction in M-protein in patients achieving ≥VGPR and PR was not significantly different in the 6-wk study period. As a predictor of VGPR, an 80% reduction in iFLC at day 21 resulted in a sensitivity of 87.5% and a specificity of 100%.

Conclusion: Changes in iFLC could be a tool for early identification of responders to anti-myeloma therapy. Early, sequential measurements of iFLC within the first week after start of treatment are not meaningful.

Keywords: half-life; immunoglobulin light chains; multiple myeloma; treatment outcome.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols*
  • Boronic Acids / administration & dosage
  • Bortezomib
  • Cyclophosphamide / administration & dosage
  • Dexamethasone / administration & dosage
  • Drug Monitoring
  • Female
  • Half-Life
  • Humans
  • Immunoglobulin Light Chains / blood*
  • Lenalidomide
  • Male
  • Melphalan / administration & dosage
  • Middle Aged
  • Multiple Myeloma / blood
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Myeloma Proteins / metabolism*
  • Prednisone / administration & dosage
  • Prospective Studies
  • Pyrazines / administration & dosage
  • Sensitivity and Specificity
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • Boronic Acids
  • Immunoglobulin Light Chains
  • Myeloma Proteins
  • Pyrazines
  • multiple myeloma M-proteins
  • Thalidomide
  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide
  • Lenalidomide
  • Melphalan
  • Prednisone