Serum Free Light Chain (FLC) Measurement in Multiple Myeloma (MM) Patients (pts) Correlate with Known Monoclonal Paraprotein, Disease Stage and Therapy Response.

So far, data based on small patient (pt) population suggest that the measurement of serum FLC from MM pts undergoing high-dose chemotherapy (HDCT) with stem cell transplantation (SCT) may be a sensitive marker for monitoring therapy success and for early detection of relapse. For further evaluation of the impact of FLCs on the assessment of treatment efficacy of standard- (ST) and HDCT with SCT, we performed a prospective analysis on serial serum specimens from 86 MM and 9 control pts. Measurement of FLC concentration was performed with the commercially available Freelite™ kit (Binding Site). For statistical analysis, pts’ clinical history, age at diagnosis, sex, current state of disease, karyotype and serum parameters, such as ß2-microglobulin, calcium levels and serum creatinine were evaluated. In the control group (NHL=6, AML=1, non-hematological disease=2), median concentrations of kappa(k)- and lambda(l)- FLC were 9.8 mg/l and 12.8 mg/l, respectively, corresponding to reference intervals for healthy individuals with normal kappa(k)/lambda(l)-ratios. In MM, 40 (46.5%) pts displayed kappa(k)-FLC levels above the upper range of 19mg/l, 26 (30%) had lambda(l)-FLC levels above the upper range of 26 mg/l and 9 pts (10.4%) had both elevated kappa(k)- and lambda(l)-FLC serum levels. An abnormal kappa(k)/lambda(l)-ratio was observed in 45 (52,3%) MM pts. Pts with a known kappa(k)-paraprotein (n=58) had a median FLC kappa(k)-concentration of 38 mg/l, but lambda(l)-FLC within the normal range. For pts with a known lambda(l)-paraprotein (n=27), reciprocal findings (76.4 mg/l for lambda(l)- vs kappa(k)-FLC in the normal range) were observed. Pts with responsive disease (CR, PR and SD) had both kappa(k)- and lambda(l)- FLC levels within the normal range, whereas newly diagnosed pts (ED) and those with PD had kappa(k)- FLC levels approx. 3-times the normal range, with lambda(l)- FLC levels at the upper limit of normal. Pts receiving ST as compared with HDCT had higher FLC levels. This is also observed in pts with amyloidosis, renal impairment or PD. Our results suggest that serum FLC assay allows monitoring of the therapy response and early detection of relapse. Determination of FLCs is also important, when evaluating new therapeutic substances, and for detection of prognostic patterns for better risk-based stratification of treatment.