Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma

J Clin Oncol. 2011 Apr 20;29(12):1627-33. doi: 10.1200/JCO.2010.33.1967. Epub 2011 Mar 14.


Purpose: To investigate the impact of immunophenotypic response (IR) versus complete response (CR) and CR plus normal serum free light chain (sFLC) ratio (stringent CR) in elderly patients with multiple myeloma (MM) treated with novel agents.

Patients and methods: From a total of 260 elderly patients newly diagnosed with MM included in the GEM05>65y trial, 102 patients achieving at least a partial response with ≥ 70% reduction in M-component after the six planned induction cycles were simultaneously analyzed by immunofixation, sFLC, and multiparameter flow cytometry (MFC) immunophenotyping; this population is the focus of this study.

Results: Forty-three percent of patients achieved CR, 30% achieved stringent CR, and 30% achieved IR. Patients in stringent CR showed no significant survival advantage compared with those in CR, whereas patients in IR showed significantly increased progression-free survival (PFS) and time to progression (TTP) compared with those in stringent CR or CR; this was confirmed by multivariate analysis (hazard ratio, 4.1; P = .01 for PFS). Discrepancies between the three techniques were relatively common. Notably, in all seven patients achieving IR but remaining immunofixation positive, the M-component disappeared in follow-up analysis. In contrast, MFC-positive patients who were immunofixation negative (n = 20) showed a tendency toward early reappearance of the M-component (median, 3 months). Similarly, in five of 11 stringent CR but MFC-positive patients, symptomatic disease progression was recorded at a median of 13 months after induction.

Conclusion: Achieving an IR translates into superior PFS and TTP compared with conventional CR or stringent CR. These techniques provide complementary information and thus, an effort should be made to refine response criteria in MM.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood*
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunoglobulin Light Chains / blood*
  • Immunologic Techniques*
  • Immunophenotyping*
  • Kaplan-Meier Estimate
  • Male
  • Multiple Myeloma / drug therapy
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / mortality
  • Nephelometry and Turbidimetry
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Spain
  • Survival Rate
  • Time Factors
  • Treatment Outcome


  • Biomarkers, Tumor
  • Immunoglobulin Light Chains