Elevated Serum Free Light Chains Are Associated With Event-Free and Overall Survival in Two Independent Cohorts of Patients With Diffuse Large B-Cell Lymphoma

Purpose The serum free light chain (FLC) assay quantitates free kappa (kappa) and free lambda (lambda) immunoglobulin light chains. This assay has prognostic value in plasma cell proliferative disorders. There are limited data on serum FLC in B-cell malignancies. Patients and Methods The association of pretreatment FLC with event-free survival (EFS) and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) was evaluated in 76 patients from the North Central Cancer Treatment Group trial N0489 (NCT00301821) and 219 patients from the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER). Published reference ranges were used to define an elevated FLC or an abnormal kappa:lambda FLC ratio. Results Elevated FLC or abnormal kappa:lambda FLC ratio was present in 32% and 14% of patients, respectively. Patients with elevated FLC had an inferior OS and EFS in both cohorts compared with patients with normal FLC (N0489: EFS hazard ratio [HR], 3.06; OS HR, 3.16; both P < .02; MER: EFS HR, 2.42; OS HR, 3.40; both P < .001; combined EFS HR, 2.57; OS HR, 3.74; both P < .001). All associations remained significant for EFS and OS after adjusting for the International Prognostic Index (IPI). Abnormal kappa:lambda FLC ratio was modestly associated with outcome in the combined group (EFS HR, 1.61; OS HR, 1.67; both P = .07), but not in patients without corresponding elevated kappa or lambda. Elevated FLC was the strongest predictor of outcome in multivariable models with the vertical bar P vertical bar components. Conclusion Increased serum FLC is an independent, adverse prognostic factor for EFS and OS in DLBCL and warrants further evaluation as a biomarker in DLBCL. J Clin Oncol 29:1620-1626. (C) 2011 by American Society of Clinical Oncology