Comparaison of Serum Free Light Chain Measurement with Classical Methods for the Evaluation of Patients with Immunoproliferative Diseases under Treatment.

Background: Therapeutic evaluation of immunoproliferative diseases requires precise quantification of the monoclonal (M) component. It currently relies on standardized methods such as serum electrophoresis or measurement of Bence-Jones proteinuria. In some cases, absence or very low level of serum and/or urinary M component hinders precise evaluation by conventional techniques. Serum quantification of free light chains (FLC) by nephelemetry, developed by Dr A. Bradwell and colleagues, has been shown to be relevant in such situations. Our study was designed to assess the usefulness of this method in the routine activity of a single institution.

Patients and methods: forty-eight consecutive patients referred to the hematology and/or nephrology department of our institution were evaluated. These patients presented with immunoproliferative diseases including multiple myeloma (n = 38) among which 20 light chain myelomas, primary amyloidosis (n = 8) and light chain deposition disease (LCDD) (n = 2). Standard electrophoresis, measurement of Bence-Jones proteinuria and serum FLC measurement (Freelite^TM, The Binding Site, Birmingham, UK) were performed in all patients with a minimum of three consecutive evaluation during treatment. The three methods were compared to determine their respective clinical benefits for clinicians.

Results: Nine patients with light chain myeloma and all patients with amyloidosis and LCDD presented with proteinuria under 0.5 g/d. In addition, 4 patients with myeloma had a serum M component below 5 g/L. Thus, difficult evaluation may be expected in 48 % of patients. Two patients failed to be evaluated by the FLC method because of normal concentrations of kappa and lambda light chains and normal kappa to lambda ratio. Thirty five percent of patients (17/48) were easily evaluated by the classical methods and no substantial additional information was obtained using serum free light chain measurement. In 21/48 (44%) of patients, for whom classical method failed to recognize any M component in serum or urine, serum FLC measurement proved very useful. For the remaining 8 patients with proteinuria < 0.5 g/d or serum M component < 5 g/l in whom evaluation with classical methods is difficult, determination of serum FLC demonstrated higher sensitivity to variations during treatment. Results were not influenced by the type of treatment. A cost-effective study shown a moderate increase in cost with Freelite^TM compared to classical methods.

Conclusion: We studied the interest of a new serum FLC measurement method in the management of patients with immunoproliferative diseases. As expected, it appears very high in patients in whom classical methods are not suitable, a common feature in patients with light chain myeloma, amyloidosis and LCDD. By contrast, patients assessable with classical techniques do not benefit from this new method. We conclude that this method can be very useful, albeit only in a minority of patients with hardly assessable immunoproliferative diseases. It is our belief that serum FLC quantification should be restricted to this subgroup of patients.