Immunophenotypic and Genetic Characteristics of Diffuse Large B-Cell Lymphoma (DLBCL), and Prognostic Significance of Cell of Origin (COO) in a Southeast Asian Cohort

Abstract BACKGROUND/OBJECTIVE: DLBCL is a heterogeneous disease which on gene expression profiling studies (GEP) can be divided into 2 distinct subtypes, germinal center (GCB) as well as activated B cell subtype (non GCB) based on the cell-of-origin. Immunochemistry (IHC) based algorithms have been shown to have good concordance with GEP for COO classification. While Western data suggests that GCB-subtypes are associated with improved outcomes, there has been limited and conflicting data on the prognostic significance of COO amongst Asian patients. The prevalence and prognostic significance of other prognostic markers such as MYC overexpression or translocation amongst DLBCL Asian patients also remains unclear. Our study aimed to evaluate i) the prevalence of MYC translocation and overexpression, as well as COO subgroups of DLBCL in a cohort of Singaporean patients, and ii) the prognostic impact of these factors in comparison with International Prognostic Index (IPI) score and other standard prognostic markers. METHODS: A single-center retrospective analysis of 384 consecutive DLBCL patients diagnosed 2013 - 2018 was performed. Hans criteria was used to assign COO. (Prior validation studies from the hospital's pathology laboratory had confirmed concordance between Hans algorithm and GEP of 75 %.) Majority of the patients received R-CHOP (N =228) or R-EPOCH (N =47) chemotherapy RESULTS: The median age of the cases was 61 years (range 18-88), 223 were female and the majority had stage 3-4 disease (62%). Of the 297 cases with IHC data for COO, 120 (40%) were GCB subtype and 177 cases (60%) were non-GCB. MYC was overexpressed in 75% of cases (165/220) tested, while MYC FISH was positive in 23% of cases (28/122) tested. 10 of the 28 patients with MYC FISH positive were treated with R-EPOCH chemotherapy. With a median follow up of 1.2 years (0.1-5.3 years), the projected 5-year OS and PFS for the entire cohort was 69.5% and 65.6% respectively. Amongst baseline clincopathologic characteristics, only age, IPI and disease stage was associated with improved OS on both univariate and multivariate analysis. Age, IPI and disease stage was associated with PFS in univariate analysis but only IPI remained significant (p<0.001) after multivariate analysis. Neither MYC overexpression, MYC translocation nor COO was found to be prognostic for OS or PFS on multivariate analysis. The 5-year PFS and OS for the GCB vs the non-GCB subgroups was 72% vs 66%, (p=0.10), and 71% vs 70%, (p=0.06) respectively. (See Figure 1A and 1B). CONCLUSION: In this Southeast Asian DLBCL cohort, we confirmed the prognostic significance of the IPI score for both PFS and OS. GCB subtype of DLBCL comprised 40% of all DLBCL cases. COO based on Hans criteria had no prognostic significance on PFS or OS. This is in contrast to Western series where GCB subtypes identified by IHC-algorithms are associated with better prognosis. Disclosures Jeyasekharan: PerkinElmer: Other: Collaboration; Merck Sharp & Dohme: Honoraria; Janssen: Research Funding; AstraZeneca: Other: Collaboration.