Changes in serum‐free light chain rather than intact monoclonal immunoglobulin levels predicts outcome following therapy in primary amyloidosis

Abstract

Current response criteria for light-chain amyloidosis (AL) relegate FLC response to a subsidiary status relative to serum M-protein response. Given that light chains form the substrate for amyloid fibril formation, we hypothesized that changes in FLC might better predict outcome compared to changes in intact immunoglobulin levels. Two patient cohorts were studied, 347 patients who underwent an autologous stem-cell transplant (SCT) and 96 patients treated with melphalan/dexamethasone. We identified the lowest value following therapy for intact serum M-protein and the difference between involved and uninvolved FLC (FLC-diff). We first examined the relative contribution of M-protein and FLC-diff on the overall survival (OS), and found that FLC reduction, rather than M-protein reduction, significantly impacted OS. The median OS was not reached among those with a 50% decrease in FLC-diff compared to 20 months for the remainder. On regression analysis, a 90% reduction in FLC-diff following SCT best predicted being alive at 3 or 5 years. The median OS among those with a 90% decrease was not reached compared to 37.4 months for the rest P < 0.001. The current study supports the notion that FLC response is a more useful measure of hematological response than M-protein response. It also highlights the importance of achieving at least a 90% reduction in the FLC-diff to improve the outcome of patients with light-chain AL. Am. J. Hematol. 86:251–255, 2011.

Serum free light-chain assay for the detection and monitoring of multiple myeloma and related conditions

“…In AL amyloidosis a higher level of sFLCs at diagnosis predicts for a higher risk of death [Kumar et al 2010]. A reduction of sFLCs on treatment appears to be more strongly related to an improvement in overall survival than intact immunoglobulin decrease after therapy [Kumar et al 2011]. Another parameter that has been recently taken into consideration in this field is the difference between involved and uninvolved sFLCs (FLCdiff), which has been incorporated into a prognostic model that also includes troponin T and N-terminal pro-B-type natriuretic peptide; this allows stratification of patients into four risk categories showing a significantly different survival [Kumar et al 2012].…”

Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements

“…12,26 However, the long-term outcome of patients with AL amyloidosis is likely to depend more on the progression of organ involvement, which in turn will depend on the continued synthesis of amyloidogenic FLC. 18,27,28 We have previously shown that serum FLC is a powerful prognostic feature in patients with AL amyloidosis. 17 In addition, we have also shown that other plasma cell clone-related factors such as the proliferation rate of plasma cells and presence of plasma cells in the peripheral circulation have prognostic value in this disease.…”

Evaluation of the N Latex free light chain assay in the diagnosis and monitoring of AL amyloidosis

“…When the FLC assay is used in conjunction with serum and urine immunofixation electrophoresis, more than 95% of plasma cell clones can be detected at diagnosis, making this combination an essential part of the work-up of patients suspected to have AL amyloidosis [1][2][3]. Changes in the FLC concentration in response to therapy have been shown to predict both organ response and overall survival (OS) [1,[4][5][6]. The importance of the FLC assay in management of AL amyloidosis is now firmly established in consensus guidelines [7][8][9].…”