Elevated monoclonal and polyclonal serum immunoglobulin free light chain as prognostic factors in B‐ and T‐cell non‐Hodgkin lymphoma

Abstract

The serum immunoglobulin free light chain (FLC) assay quantitates free kappa (κ) and lambda (λ) light chains. FLC elevations in patients with diffuse large B-cell lymphoma (DLBCL), Hodgkin lymphoma (HL), and chronic lymphocytic leukemia (CLL) are associated with an inferior survival. These increases in FLC can be monoclonal (as in myeloma) or polyclonal. The goal was to estimate the frequency of these elevations within distinct types of B-cell and T-cell non-Hodgkin lymphoma (NHL) and whether the FLC measurements are associated with event-free survival (EFS). We studied serum for FLC abnormalities using normal laboratory reference ranges to define an elevated κ or λ FLC. Elevations were further classified as polyclonal or monoclonal. 492 patients were studied: 453 B-cell and 34 T-cell NHL patients. 29% (142/453) had an elevated FLC of which 10% were monoclonal elevations. Within B-cell NHL, FLC abnormalities were most common in lymphoplasmacytic lymphoma (79%), MCL (68%) and MALT (31%); they were least common in FL (15%). The hazard ratio (HR) for EFS in all patients was 1.41 (95% CI; 1.11–1.81); in all B-cell NHL the HR was 1.44 (95% CI 1.11–1.96); in all T-cell NHL the HR was 1.17 (95% CI 0.55–2.49). FLC abnormalities predicted an inferior OS (HR = 2.75, 95% CI: 1.93–3.90, p<0.0001). The serum FLC assay is useful for prognosis in both B-cell and T-cell types of NHL. In B-cell NHL further discrimination between a monoclonal and polyclonal elevation may be helpful and should be analyzed in prospective clinical trials.

Cohort Profile: The Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource (MER) Cohort Study

“…Elevated serum free light chains (FLC) or an abnormal FLC ratio was associated with an inferior EFS and OS in DLBCL 41 and HL; 42 shorter time to treatment and inferior OS in CLL; 43 and inferior EFS in FL grade 3, mantle cell and other low-grade B-cell lymphomas and peripheral Tcell lymphoma not otherwise specified (PTCL-NOS). 44 DLBCL patients with elevated pre-treatment serum levels of interferon-inducible protein-10 (CXCL10) had inferior EFS and OS even after adjustment for the International Prognostic Index. 45 Elevated pre-treatment serum levels of the pro-inflammatory cytokines IL-2R, IL1-R1 and CXCL9 were associated with inferior EFS in FL.…”

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

“…This includes intact Igs comprising bound heavy light chains (HLC) and unbound free light chains (FLC) due to more abundant light-chain synthesis. Abnormal polyclonal (κ + λ) or monoclonal (κ/λ) FLCs in serum have been shown to be biomarkers of prognosis and survival in plasma cell disorders 14–18 and other B-cell lymphoid malignancies, including CLL 19–24 . Prospective cohorts have identified elevated polyclonal and abnormal monoclonal FLCs as early biomarkers of CLL, detectable upto 9.8 years before diagnosis 25 .…”

Serum Free Light Chain Assay as a Prognostic Marker in Patients with Aggressive B-Cell Non-Hodgkin's Lymphoma: Impact on Survival Outcome

“…In the study by Witzig et al, 2 out of 453 patients with B-cell NHL, 27.8% had an elevated FLC with 17.4% polyclonal and 10.4% monoclonal in origin. In our study, 38% had elevated FLC of which 26% had polyclonal elevation and 12% had monoclonal elevation.…”