Diffuse large B-cell lymphoma: therapeutic development based on clinical and biological heterogeneity

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, and is regarded as a heterogeneous group of lymphomas in terms of morphologic, immunologic, and cytogenetic features. The current standard therapy for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy, which allows many patients to achieve disease cure. Despite recent progress in improving patient survival, 40% of DLBCL outcomes are still unsatisfactory. Gene expression profiling has been used to identify two distinct forms of DLBCL: the activated B-cell (ABC) subtype and the germinal center B-cell (GCB) subtype, which reflects normal B-cell differentiation. ABC DLBCL has been reported to show a more activated phenotype and a poorer prognosis than the GCB subtypes, with molecular diagnosis after R-CHOP therapy. Next generation sequencing identified unique oncogenic mechanisms and genetic complexity, which provided rational therapeutic targets. Recent studies suggest that patients with double-hit lymphoma, i.e., dual rearrangements of MYC and BCL2, have an extremely grim prognosis. Moreover, there are a number of biomarkers including CD5 and prognostic factors. Efforts to distinguish among these biomarkers will be crucial for devising individualized treatments in the future.