Identifying aggressive subsets within diffuse large B-cell lymphoma: implications for treatment approach.

Clinical and pathological risk stratification has long been the standard for identifying likelihood of future disease progression and overall survival; however, these prediction models lack the granularity of individual patient pathology and response to therapy. Molecular subtypes defined through whole exome sequencing have independent prognostic significance. While identifying molecular drivers of aggressive disease has provided the opportunity to analyze novel therapy combinations with front-line chemoimmunotherapy, only modest benefit has been observed when targeting DLBCL subtypes. Combining clinical, pathologic, and molecular data will likely result in significant improvement in our ability to identify the most aggressive DLBCL subsets. Novel therapies and trial designs will continue to play an important role as we target these at-risk populations in the future.