The Serum Free Light Chain Ratio after One or Two Cycles of Treatment Is Highly Predictive of the Magnitude of Final Response in Patients Undergoing Initial Treatment for Multiple Myeloma.

BACKGROUND: The serum free light chains assay (FLC) has recently become commercially available for use in the management of multiple myeloma. This assay is more sensitive for the detection of monoclonal light-chains than previously available tests and has therefore found many unique applications. It can detect two-thirds of non-secretory multiple myelomas that were previously missed by immunofixation; it permits a more sensitive detection of monoclonal FLCs in AL amyloidosis; and it may allow earlier identification of disease recurrence in multiple myeloma and amyloidosis patients after treatment. We have sought to examine the usefulness of this assay as an early predictor of final response in patients with symptomatic multiple myeloma undergoing initial therapy.

METHODS: We have performed an analysis of FLC assay in forty-five patients who were enrolled in an IRB approved phase II clinical trial whose main objectives were to determine the efficacy and toxicity of the administration of doxorubicin and dexamethasone, followed by thalidomide and dexamethasone in patients with untreated multiple myeloma (ASH 2004). The response to treatment was assessed based on the EORTC consensus criteria. Using Fisher’s exact test, we have evaluated the association between the status of the FLC ratio after cycle one and cycle two (i.e. normalized or persistently abnormal) and the status of response at the completion of 5 cycles of treatment, in patients with an abnormal FLC ratio at baseline (normal range 0.26 – 1.65).

RESULTS: Of the 42 patients evaluable for response, 37 had an abnormal free light chain ratio at baseline (i.e. < 0.26 or > 1.65). Normalization of the FLC ratio after cycle one or cycle two occurred in seven out of 15 patients who achieved near complete remission (nCR) or complete remission (CR), and only in one of 22 patients who achieved partial remission (PR), stable disease (SD), or progression of disease (POD). Among the eight patients who had normalization of the FLC ratio after one or two cycles of treatment, seven achieved nCR or CR and one achieved PR. Normalization of the FLC ratio after one or two cycles of treatment was significantly associated with the achievement of CR or nCR (p=0.003).

CONCLUSION: Normalization of the free light chain ratio after the first or the second cycle of treatment is highly predictive of achievement of nCR or CR at the completion of treatment. If this observation is confirmed in larger studies and for other regimens, the assessment of the free light chain ratio after two cycles may become an important milestone in the decision making for patients with multiple myeloma undergoing initial therapy. Since the aim of therapy is to achieve nCR or CR, the addition of alternative drugs might be advisable at an early stage of treatment in patients whose free light chain ratio remains abnormal.