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

Abstract

Purpose: The serum free light chain (FLC) assay quantitates free kappa (κ) and free lambda (λ) 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 κ:λ FLC ratio.

Results: Elevated FLC or abnormal κ:λ 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 κ:λ 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 κ or λ. Elevated FLC was the strongest predictor of outcome in multivariable models with the IPI 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.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Pretreatment serum free light chain values (mg/dL) from North Central Cancer Treatment Group N0489 and Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) cohorts. Dashed box indicates normal range.

Fig 2.

(A) Event-free survival and (B) overall survival Kaplan-Meier survival curves by serum free light chain (FLC) in two cohorts (North Central Cancer Treatment Group trial N0489 and the Specialized Program of Research Excellence Molecular Epidemiology Resource [MER]) of patients with untreated diffuse large B-cell lymphoma.

Fig A1.

Outcome by type of free light chain (FLC) abnormality. (A) Event-free survival; (B) overall survival.

Fig A2.

Estimated hazard ratios (blue lines) and 95% CIs (gray lines) across the range of values for kappa, lambda, and total free light chain (FLC) from P-spline models for overall and event-free survival. (A, C, E) Risk of event; (B, D, F) risk of death.

Fig A3.

Time-dependent area under the curve (AUC) of free light chain (FLC) compared with International Prognostic Index (IPI) alone and a model with both FLC and IPI. (A) Event-free survival; (B) overall survival. LDH, lactate dehydrogenase; ULN, upper limit of normal; PS, performance status.

Fig A4.

Serial free light chain measurements in a patient with a lambda-restricted tumor who relapsed 9 months after treatment. PET, positron emission tomography; Pos, positive; Neg, negative.