Prognostic utility of intact immunoglobulin Ig′κ/Ig′λ ratios in multiple myeloma patients

To determine whether isotype matched immunoglobulin (Ig; Ig 'kappa/Ig 'lambda) ratios had prognostic significance in patients with intact Ig multiple myeloma (MM). Novel immunoassays measuring serum concentrations of the Ig heavy chain/light chain (HLC) subsets IgG kappa, IgG lambda, IgA kappa and IgA lambda were compared with monoclonal protein ('M-spike') quantification by serum protein electrophoresis, beta(2)-microglobulin (beta(2)-M), albumin, serum free light chain (FLC) and cytogenetic markers in relation to outcome in 339 MM patients. Abnormal IgG kappa/IgG lambda and IgA kappa/IgA lambda ratios present in the respective tumor isotypes at clinical presentation were predictive of shorter progression-free survival (PFS) (hazard ratio (HR) 1.9; P = 0.0002), predominantly due to the suppression of the uninvolved (polyclonal) Ig of the same isotype as the tumor (HR 1.8; P = 0.002). No significant associations were observed between PFS and M-spike concentrations, suppression of non-tumor Igs of different isotypes or FLC kappa/lambda ratios. beta(2)-M and HLC ratios were independently prognostic (P = 0.045 and P = 0.001). A staging system using beta(2)-M and extreme HLC ratios (<0.01 or >200) had greater prognostic value than the widely used ISS staging system (HR 1.7; P = 0.00002 vs HR 1.3; P = 0.017). These results suggest that HLC ratios may have a role in clinical management of MM. Leukemia (2013) 27, 202-207; doi: 10.1038/leu.2012.159