Prognostic utility of intact immunoglobulin Ig'kappa/Ig'lambda ratios in multiple myeloma patients
Bradwell A et al. – HLC ratios may have a role in clinical management of MM.Methods
- Novel immunoassays measuring serum concentrations of the Ig heavy chain/light chain (HLC) subsets IgGkappa, IgGlambdo, IgAkappa and IgAlambda were compared with monoclonal protein (‘M-spike’) quantification by serum protein electrophoresis, beta2-microglobulin (beta2-M), albumin, serum free light chain (FLC) and cytogenetic markers in relation to outcome in 339 MM patients.
- Abnormal IgG?/IgG? and IgAkappa/IgAlambda 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.
- beta2-M and HLC ratios were independently prognostic (P=0.045 and P=0.001). A staging system using beta2-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).