Serum free light chains for monitoring multiple myeloma

Prior studies have demonstrated the utility of serum free light chains (FLC) in the diagnosis and monitoring of non-secretory (Drayson et al, 2001) and light chain myeloma (LCMM) (Bradwell et al, 2003). Mead et al (2004) have also suggested a role in myelomas that produce an intact immunoglobulin paraprotein (IIMM), where 96% of patients had an abnormal FLC ratio and/or monoclonal FLC concentration at diagnosis and it was concluded that serum FLC assays could be used to follow the disease course in nearly all multiple myeloma patients. We have reservations, however, regarding the broader application of FLC monitoring to patients with IIMM, in particular to the use of the FLC assay in monitoring for disease relapse post-autologous stem cell transplantation. We assessed whether the serum kappa to lambda (K/L) FLC ratio might be an early predictor of disease progression in patients with IIMM following autologous stem cell transplantation. Sera of patients with IIMM or LCMM who underwent autologous transplantation and were in complete remission or plateau phase were analysed. The FLC concentration was measured using a kit assay (The Binding Site Ltd, Birmingham, UK) and the Immage (Beckman Coulter, Brea, CA, USA) protein system. Monoclonal paraprotein was detected by serum protein electrophoresis (Beckman Coulter) and/or immunofixation (IFE). Myeloma response and relapse were defined according to international criteria (Bladé et al, 1998). Thirty-four patients were monitored post-transplant, on an average bimonthly, for a median of 16 months (range, 3–36 months). K/L FLC ratios were within the manufacturer’s reference interval for IIMM and LCMM patients in complete remission (0Æ41–1Æ59; n 1⁄4 15) except for one LCMM patient (K/L ratio 0Æ15) with no Bence Jones protein detected on IFE and 2% polyclonal plasma cells on bone marrow biopsy. Seventy-two per cent (13/18) of IIMM and LCMM patients in plateau phase (i.e. residual serum paraprotein ranging from <1 to 19 g/l or trace Bence Jones proteinuria) had a normalised FLC ratio (0Æ39–1Æ49) with four patients having abnormal ratios (0Æ16, 0Æ23, 0Æ24, 3Æ4, 5Æ5). Eleven patients with IIMM have relapsed. Whereas the FLC ratio and monoclonal FLC concentration have been reported to reflect changes in disease progression in LCMM (Bradwell et al, 2003), we did not observe the same correlation in IIMM (Table I). Of 11 relapsed IIMM patients, four had persisting normal FLC concentrations and ratios, despite rising paraprotein concentrations of 10–36 g/l and abnormal bone marrow biopsy (plasma cells 9–100%). In two other patients, increasing paraprotein concentration (IgA lambda 1Æ7–23 g/l; IgG kappa 11–27 g/l) preceded increasing monoclonal lambda FLC concentration (14–35 mg/l, ratio 0Æ96–0Æ29) and kappa FLC concentration (60–75 mg/l, ratio 5Æ5–11Æ9) by 8 and 4 months respectively. In another, increasing lambda FLC (40–179 mg/l; ratio 0Æ49–0Æ05) preceded an increase in paraprotein (19–31 g/l) by 11 months, and in four others, serum paraprotein and monoclonal FLC concentration increased simultaneously. Thus, 55% (6/11) of our transplanted group failed to give an abnormal ratio or elevated FLC concentration at or prior to disease relapse. Our data suggest that serum FLC measurement may not be useful as an early predictor of disease reoccurrence compared with the serum paraprotein in patients with IIMM posttransplantation. Systematic study of the role of FLC monitoring needs to occur in the context of larger prospective studies before it is routinely applied to the monitoring of patients with IIMM.