Clinical implications of the molecular subtypes of diffuse large B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and responds to standard treatment with chemoimmunotherapy in most patients. Standard prognostic scoring systems such as the International Prognostic Index (IPI) are useful for risk stratification, but are unreliable in predicting outcomes in individual patients because of the biologic heterogeneity of this disease. Gene expression profiling has revealed molecular subtypes of DLBCL: those derived from the lymph node germinal center (GCB) and others derived from an activated B-cell (ABC). A third entity, primary mediastinal B-cell lymphoma (unclassifiable DLBCL), displays pathobiologic features distinct from ABC and GCB subtypes. Patients with ABC-DLBCL have inferior progression-free survival and overall survival relative to those with the GCB subtype. In conclusion, molecular subtyping is a powerful tool for discriminating cases of DLBCL into groups that display very disparate biology and clinical outcomes. Although immunohistochemistry (IHC)-based algorithms predict both the molecular subtype as defined by gene expression profiling and clinical outcomes with reasonable concordance, not all experienced centers have been able to reproduce these findings. As techniques to subclassify DLBCL become universally adopted, large prospective trials will be needed to confirm the benefit of therapy tailored to molecular subtype.