Introduction
Diffuse large B-Cell lymphoma (DLBCL) is the most common type of Non Hodgkin Lymphoma (NHL) constituting 30-40% of cases (1,2,3). An estimated 27,650 new cases were diagnosed in 2016 with 25,380 of them being the not otherwise specified (NOS) variant (4). DLBCL shows a slight male predominance (55%) and the median age at diagnosis is 64 years, but the disease affects all age groups and age of onset is earlier in African Americans (5,6). The 5-year survival rate shows mild geographic variation, 62% in the US (7) and 55.4% in Europe (8).
DLBCL, despite its relative morphologic homogeneity, represents heterogeneous entities, with disparate biological and clinical manifestations. Outcome of disease to standard first line therapy, R-CHOP, consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone plus the monoclonal antibody rituximab, is variable. Twenty to fifty percent of patients are either refractory to therapy without remission or relapse after complete remission (9,10,11)
Relapsed disease is associated with a poor prognosis and patients with early disease relapse have a worse prognosis compared to those with late relapses (12). The mechanisms for relapse are purportedly different for these two groups (13). The prognosis for refractory patients, patients whose disease fails to go into remission or progress with induction therapy, is even more dismal compared to early and late relapse disease (14). While patients with relapse and refractory disease might have had need for more aggressive first line therapies, there are currently no biomarkers that adequately predict at diagnosis, the patients who are likely to be refractory to therapy, relapse after initial remission, or the time of relapse whether early or late. Similarly, once treatment commences or remission is achieved, there are no biomarkers that can accurately predict subsequent behavior of the disease. In addition, in refractory and relapsed disease, biomarkers capable of predicting response to second or additional lines of therapy remain elusive. Thus, there exists an urgent, unmet clinical need for biomarkers that address these challenges in management of DLBCL.
Current disease stratification systems/methods and assays