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