Serum-free light chain—a new biomarker for patients with B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia

Abstract

New nephelometric immunoassays specific for free immunoglobulin light chains (FLCs) improve detection of monoclonal proteins (M-protein). Initial studies with FLC have focused on multiple myeloma and amyloidosis. The goal of this study was to evaluate the frequency of monoclonal serum FLC in patients with other B-cell malignancies. Frozen sera from 226 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) were tested for M-protein by the serum FLC assay and compared with standard protein electrophoresis (PEL) and immunofixation (IF). Overall, 24% (54/226) of samples had a detectable M-protein with 63% of these (34/54) FLC-positive. In 35% (19/54), the M-protein was only detectable by FLC analysis. Of the 208 NHL patients, 22% (46/208) had a detectable M-protein. Also, 13% (27/208) were positive for FLC and 16% (33/208) had a detectable M-protein by PEL/IF. Twenty-eighty percent (13/46) of NHL patients with M-proteins were detectable only by FLC analysis. Within NHL, the highest incidences of FLC presence were in patients with mantle cell (36%) and small lymphocytic (24%). Among CLL patients, 44% had an M-protein with 39% detected by FLC and 11% detected by PEL/IF. Notably, in 6 of 8 CLL patients, the M-protein was only detectable by the FLC method. Serum FLC can be detected in a substantial fraction of patients with NHL/CLL, and the FLC technique improves detection of M-proteins when combined with standard PEL/IF. Future studies are warranted to elucidate the role of serum FLC as biomarkers of disease, for monitoring of minimal residual disease, and as a prognostic factor for response and survival.