Cell-of-origin of diffuse large B-cell lymphomas determined by the Lymph2Cx assay: better prognostic indicator than Hans algorithm

Abstract

Diffuse large B-cell lymphomas (DLBCLs) are clinically heterogeneous and need a biomarker that can predict the outcome of treatments accurately. To assess the prognostic significance of the cell-of-origin type for DLBCLs, we applied the Lymph2Cx assay using a NanoString gene expression platform on formalin-fixed paraffin wax-embedded pretreatment tissues obtained from 82 patients with de novo DLBCL, not otherwise specified. All patients were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as the first line of chemotherapy. Based on the expression levels of Bcl-6, CD10, and MUM-1 measured by immunohistochemistry, cases were subdivided into germinal center B-cell (GCB) and non-GCB types according to the Hans algorithm. NanoString assay was performed on 82 cases. The Lymph2Cx assay successfully classified 82 cases into three categories: activated B-cell (ABC), GCB, and unclassified types. The concordance rate between the Lymph2Cx assay and the Hans algorithm was 73.6%. The Lymph2Cx-defined ABC type had significantly poorer outcomes compared with the GCB type (5-year overall survival, GCB vs. ABC, 96.6% vs. 77.1%, P = 0.020; 5-year disease-free survival, GCB vs. ABC, 96.6% vs. 79.2%, P = 0.018). In contrast, no significant differences were observed in survival between the two patient subgroups with DLBCL types classified by the Hans algorithm. The Lymph2Cx assay is a robust, reliable method for predicting the outcome of patients with DLBCL treated with R-CHOP chemotherapy.

Keywords: Lymph2CX; diffuse; gene expression profiling; large B-cell; lymphoma.

Figure 1. Kaplan–Meier analysis of 5-year OS and DFS in the patients with DLBCL types classified by the Hans algorithm A., C. or the Lymph2Cx assay B., D

(A) COO assay by the Hans algorithm showed no difference in 5-year OS (P = 0.749) between GCB and non-GCB types. (B) Lymph2Cx-defined GCB type gave the most favorable outcome among three Lymph2Cx-defined subgroups (GCB vs. ABC vs. unclassified; 96.6% vs. 77.1% vs. 60%, respectively; P = 0.026). (C) COO assay by the Hans algorithm showed no difference in the 5-year DFS rate (P = 0.155) between the GCB and non-GCB types. (D) The Lymph2Cx-defined GCB type had the best patient survival among the three subgroups (GCB vs. ABC vs. unclassified; 96.6% vs. 79.2% vs. 60%, respectively; P = 0.021).