MEASUREMENT OF FREE KAPPA-CHAIN AND LAMBDA-CHAIN IN SERUM AND THE SIGNIFICANCE OF THEIR RATIO IN PATIENTS WITH MULTIPLE-MYELOMA

An inhibition enzyme-linked immunoassay technique using commercially available antibodies has been developed for the quantitation of both kappa and lambda light chains in the serum of patients with B-cell malignancies. Assay conditions were selected to enable measurement of free light chains in the concentration range between 0.1 and 20 mg/l. The normal range for free lambda chains in serum was found to be 0.4-4.2 mg/l and for free kappa chains it was 1.6-15.2 mg/l. At diagnosis the serum of most patients with multiple myeloma contained increased levels of the malignant free light chain and in some cases there was also elevation of the non-malignant light chain. The absolute level of the malignant light chain at diagnosis did not correlate with survival nor with laboratory parameters such as IgM or creatinine. A correlation with beta-2M and serum paraprotein levels was evident only in cases of IgA myeloma. Although the absolute level of free serum light chain had no value as a prognostic indicator. the ratio of kappa:lambda chains closely followed the clinical assessment of disease status, being near the normal range (1.2-9.1) in plateau phase or stable disease. During periods of progressive disease this ratio ranged from 19 to 460 (n = 14) in patients with kappa myeloma, and 0.001 3-0.14 (n = 9) in patients with lambda myeloma. Determination of the ratio of free light chains in the serum may allow effective monitoring and earlier warning of disease progression in patients with multiple myeloma.