Diffuse large B- cell lymphoma is a common label for a number of clinico- pathological entities, which differ in molecular pathogenesis, clinical presentation and prognosis. Exact correlation between clinico- pathological and molecular subtypes of diffuse large B- cell lymphoma was not optimally defined; however, key signal transduction pathways were identified; blockage of these pathways may be therapeutically significant.
The purpose of this review is to show current approach to diagnostics of diffuse large B- cell lymphoma on molecular levels, to summarize current first-line treatment options for newly diagnosed diffuse large B- cell lymphoma patients and to introduce new treatment possibilities, which are currently under investigation in clinical trials.
Current molecular diagnostics of diffuse large B- cell lymphoma is evolving in two main directions. One direction is classification according to gene expression or protein levels. According to these studies, patients may be divided into subgroups according to the cell of origin or according their stromal signature. Most frequently used is classification according cell of origin (COO), which divides diffuse large B-cell lymphomas into GCB subtype (germinal B-cell like) or ABC subtype (activated B-cell like). Second direction is studying genetic information on DNA level, where genetic mutations, deletions, amplifications and losses of heterozygozity are identified, which may be specific for subgroups defined by gene expression analysis, but may go across them. Both these directions aim at identifying signaling pathways important for survival and proliferation of tumor cells and in these, to identify targets for pharmacological blockage. Currently, standard of first-line treatment for all patients is antracycline-based regimen with rituximab, which improved prognosis in both cell of origin subtypes, even if patients in the ABC subgroup have still inferior outcome. There is a number of new drugs with promising effectivity, which are studied in different phases of clinical trials (lenalidomide, bortezomib, idelalisib, venetoclax), but their possible effectivity will be limited only for precisely defined molecular subtypes of diffuse large B- cell lymphoma.
The advent of new targeted drugs for diffuse large B- cell lymphoma is still awaited. For their effective use, besides the proof of their effectivity in randomized studies, also the extension of use of molecular methods in routine diagnostics and ensuring their wide availability will be necessary.