Early Serum Free Light Chain Responses Following High-Dose Melphalan and Stem Cell Transplantation for AL Amyloidosis.

Abstract 4352

AL amyloidosis is a clonal plasma cell dyscrasia which produces insoluble amyloid fibrils from Ig light chains, leading to multiorgan failure. High dose melphalan and autologous stem cell transplantation (HDM/SCT) can induce remission and extend survival, but response is assessed at 6 and 12 months. Serum free light chain (FLC) assays can improve detection of AL amyloidosis, have prognostic significance, and are routinely used to assess response to treatment. Serum half life of FLCs is only 2-6 hours, even with diminished glomerular filtration rates. In a small prospective series, we previously reported that FLC levels 1-3 weeks after HDM/SCT correlate with hematologic response at 1 year. This study was performed to confirm these results on a larger scale. A prospective analysis of patients with AL amyloidosis treated with HDM/SCT was performed to determine the extent to which early FLC responses predict hematologic complete response (CR). Exclusion criteria included initial normal FLC concentrations and ratios and chronic renal insufficiency (Cr>1.2 mg/dL) with a normal FLC ratio. Hematologic responses, as defined by standard traditional criteria, were determined at 6 and 12 months. Traditional criteria define hematologic CR as by normalization of bone marrow exam and absence of monoclonal gammopathy in urine and serum by immunofixation electrophoreses. Serum FLC concentrations were measured by a sensitive nephelometric analysis within 10 days and within 3 weeks of HDM/SCT. Complete response for serum FLC was defined as normalization of FLC concentration and ratio or normalization of the ratio in renal failure (Cr>1.2 mg/dL). Serum FLC levels or k/l FLC ratios were abnormal and informative in 124 patients (87%) prior to HDM/SCT, and these patients were included in subsequent analyses. One week after transplant, sensitivity of FLC to predict hematologic CR was 0.64, specificity was 0.67, positive predictive value (PPV) was 0.49, negative predictive value (NPV) was 0.79, positive likelihood ratio (LR) was 1.92, and negative LR was 0.54. For a >90% reduction in FLC, sensitivity to predict hematologic CR was 0.36, specificity was 0.86, PPV was 0.54, NPV was 0.75, positive LR was 2.59, and negative LR was 0.74. Two to three weeks after transplant, sensitivity of FLC CR to predict hematologic CR was 0.72, specificity was 0.74, PPV was 0.57, NPV was 0.85, positive LR was 2.78, and negative LR was 0.38. For a >90% reduction in FLC, sensitivity to predict hematologic CR was 0.34, specificity was 0.86, PPV was 0.52, NPV was 0.74, positive LR was 2.40, and negative LR was 0.77. Serum FLC concentrations within 3 weeks of HDM/SCT have poor predictive values and should not be used to predict hematologic CR. However, failure to reduce FLC concentrations by 90% has a somewhat higher negative predictive value and could be used to guide additional post-transplant management.