Evaluation of the serum free light chain (sFLC) analysis in prediction of response in symptomatic multiple myeloma patients: rapid profound reduction in involved FLC predicts achievement of VGPR

BACKGROUND: Observational data from clinical studies indicate that the goal of first-line therapy in newly diagnosed patients with symptomatic multiple myeloma (MM) should be very good partial response (VGPR) or better, preferably before high-dose treatment. We evaluated the value of early measurements of involved free light chains (iFLC) in prediction of high-quality responses. Measuring iFLC has a potential advantage due to a short half-life compared to the half-life of the M-protein. METHODS: In 36 multiple myeloma (MM) patients, we measured serial changes in iFLC and M-protein after start of treatment. iFLC and M-protein were measured before treatment, the following 5 wk days, 2, 3 and 6 wks after start of treatment. RESULTS: Median iFLC and M-protein half-life was 2.75 and 11.9 d, respectively. All patients with an iFLC >75 mg/L had an initial significant reduction (>20%) in iFLC, even patients with no response to treatment. The mean per cent reduction in iFLC 3 d after start of treatment was 52.3% and 23.6% (P = 0.021) in patients achieving ≥VGPR and PR, respectively. The mean per cent reduction in M-protein in patients achieving ≥VGPR and PR was not significantly different in the 6-wk study period. As a predictor of VGPR, an 80% reduction in iFLC at day 21 resulted in a sensitivity of 87.5% and a specificity of 100%. CONCLUSION: Changes in iFLC could be a tool for early identification of responders to anti-myeloma therapy. Early, sequential measurements of iFLC within the first week after start of treatment are not meaningful.