title: Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients.
abstract: The novel heavy/light chain (HLC) assay was used for the detection and measurement of monoclonal immunoglobulins, response evaluation and prognostication. This test allows identification and quantification of the different light chain types of each immunoglobulin class (for example, IgGκ and IgGλ) and enables calculation of ratios of monoclonal/polyclonal immunoglobulin (HLC ratio). Sequential sera of 156 patients with IgG or IgA myeloma started on first-line therapy and followed for a median of 46.1 months were analyzed. Results were compared with those obtained with conventional techniques (serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), nephelometry (NEPH), and the free light chain test (FLC)). Our data show that the HLC assay allowed quantification of monoclonal proteins not accurately measurable by SPEP or NEPH. When both HLC and FLC testing were applied for response assessment, clonal excess was noted in 14/31 patients with complete response (CR). HLC ratio indicated presence of disease in 8/31 patients who achieved CR and, in sequential studies indicated evolving relapse in three patients before IFE became positive. Highly abnormal HLC ratios at presentation were significantly associated with shorter overall survival (40.5 months vs median not reached, P=0.016). Multivariate analysis revealed HLC ratio (P=0.03) and β(2)-microglobulin (P<0.01) as independent risk factors for survival.
authors.affiliation: Wilhelminenhospital Department of Medicine I, Center for Oncology and Hematology, Wilhelminenspital, Vienna, Austria. heinz.ludwig@wienkav.at
authors.forename: H
authors.initials: H
authors.lastname: Ludwig
authors.forename: D
authors.initials: D
authors.lastname: Milosavljevic
authors.forename: N
authors.initials: N
authors.lastname: Zojer
authors.forename: J M
authors.initials: JM
authors.lastname: Faint
authors.forename: A R
authors.initials: AR
authors.lastname: Bradwell
authors.forename: W
authors.initials: W
authors.lastname: Hübl
authors.forename: S J
authors.initials: SJ
authors.lastname: Harding
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001797:Blood Protein Electrophoresis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007122:Immunoelectrophoresis; D007143:Immunoglobulin Heavy Chains / Q000097:blood*; D007132:Immunoglobulin Isotypes / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000097:blood*; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D009101:Multiple Myeloma / Q000097:blood* / Q000628:therapy; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D010265:Paraproteinemias / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains