Therapy Response by Decrease of Free Light Chain Concentration in Multiple Myeloma Patients Treated with Bortezomib/Doxorubicin/Dexamethasone as First-Line Therapy.

Incorporation of new drugs such as the proteasome inhibitor bortezomib in the treatment of multiple myeloma (MM) has increased response rates. However, the challenge is to find the optimal combination of drugs and to change therapy as early as possible in case of suboptimal response. Therefore, we analyzed retrospectively the concentrations of serum free light chains (FLC) before, during and after therapy with bortezomib/doxorubicin/dexamethasone. In order to evaluate their prognostic value we compared the FLC kinetics to therapy response according to the International Uniform Response Criteria. Sixteen patients with newly diagnosed symptomatic MM (IgG/kappa: 9, IgG/lambda: 2, IgA/lambda: 1, IgA/kappa: 1, IgD/lambda: 1, IgD/kappa: 1, light chain kappa: 1) who received 4 cycles of bortezomib/doxorubicin and dexamethasone as initial therapy from November 2005 to June 2007 were analyzed. All patients showed a decrease in the FLC and/or a change of the quotient kappa/lambda towards the normal value after therapy. Reduction of FLC concentration ranged from 2.4- to 840-fold. Marked reduction could be observed after the first cycle of therapy. Seven patients revealed good response (sCR, CR or VGPR). In six of them, the decrease in FLC concentration was at least 20-fold, in one patient 2.9-fold. This patient had only a moderate increase of FLC concentration before therapy (below four times upper limit of normal). Two patients did not achieve good response (SD: 1, PD: 1); they had only a slight reduction in FLC (2.4- and 2.5-fold, respectively) although their initial FLC concentration was high. In parallel to the reduction of FLC, the serum concentration of immunoglobulins decreased. However, lowering of FLC occurred earlier and was more pronounced. Measurement of FLC concentration provides more rapid information for treatment monitoring than immunoglobulins and thus may be helpful to change therapy as early as possible in case of suboptimal response.