Differences in the Clinicopathological Feature, Prognostic Features and Treatment Outcomes between Molecular Subtypes Among Indian Cohort with Diffuse Large B-Cell Lymphoma - a Single Center Experience

Background: Diffuse Large B cell Lymphoma (DLBCL) accounts for nearly 25% of all Non-Hodgkin's lymphoma (NHL) in the developed world, making it the most common lymphoma. With the diversities in clinical presentation, morphology, molecular and genetic alterations, DLBCL represents a heterogeneous group rather than a single disease entity. Based on the cell-of-origin (COO) concept, gene expression profiling (GEP) has identified two major subtypes of DLBCL with differing prognoses. We aim to study the trends in the clinico-pathological features, prognostic factors and treatment outcomes following standard therapy between the molecular subtypes.

Methods: A prospective study with 243 consecutively diagnosed cases of DLBCL between September 2009 and April 2017 were included. The clinico-pathological features, IPI score, extranodal involvement and stage of disease were recorded using a predesigned proforma. All patients received Rituximab based treatment which was modified according to their tolerability. Molecular subtyping to GCB and ABC subtype was performed using immunohistochemistry.Primary objective was to assess the clinico-pathological features, prognostic factors and differences between the molecular subtypes in Indian population. Secondary objective was to study the overall progression free survival (PFS).

Results: Out of 243 patients enrolled in the study, 47% (n=129) were > 60 years, the median age being 55 years. Majority were males (63%). Fever (28%), pain abdomen (11%), weight loss (30%) and painless neck swelling (26%) were the most common symptoms. Nodal presentation was more common than extranodal [56.4% (n=137) versus 43.7% (n=106) respectively]; stomach (12.2%) being the most common extranodal site. 22.6%(n=55) high intermediate and 38.3% (n=93) with high IPI score. Bone marrow involvement was detected in 23% population (n=56). 51% (n=124) were diagnosed as stage IV, 24.3% (n=59) stage III, 16% (n=39) stage II and 8.6% (n=21) in stage I. Molecular subtyping was performed in 198 patients (81.4%) with GCB subtype seen in 45.5% (n=90) and ABC in 54.5% (n=108). 62.6% achieved complete metabolic response (CMR) and 18.9% (n=39) had disease progression. ABC subtype had more extranodal presentation [(54.6%, n=59 v/s 35.6%, n=32); p=0.007]. More number of disease progressions [17.8%; n=18 v/s 10.1%, n=9] and deaths [11.9%; n=12 v/s 3.4%, n=3]; p=0.046 were recorded in ABC Subtype. High IPI Score was seen in ABC subtype [45.6%, n=47 v/s 28.1% [n=25], p=0.063. Median survival time of patients was 81 months + SE 1.705 [CI 72.26-78.95]. There was a significant difference in the median PFS among those whose did not progress versus those who did [87.22 months v/s 72.66 months]. ABC subtype, high LDH Levels > 618 and patients with higher stage at presentation had disease progression. In this study, using both univariate and multivariate cox regression model, no risk factor was found to be associated with survival.

Conclusions: R-CHOP remains the standard of care for patients with DLBCL. However, literature reports a cure rate of only 60% with standard immuno-chemotherapy with 40% eventually dying of the relapsed disease. DLBCL can no longer be considered and treated as one disease. It is imperative to identify those molecular and prognostic markers that would identify subset of patients who would benefit from a more aggressive course.