Front-Line Treatment of High Grade B Cell Non-Hodgkin Lymphoma

Purpose of Review Rituximab-based chemoimmunotherapy has resulted in a marked improvement in the survival of diffuse large B cell lymphoma (DLBCL). We reflect upon the history front-line (1L) therapy and highlight advances in management. Recent Findings Since the introduction of R-CHOP, the majority of randomized studies in the front-line treatment of DLBCL have failed to show a benefit. Such studies have involved treatment intensification, adding novel agents to the R-CHOP backbone and targeting such novel agents to biologically defined subgroups. R-CHOP therefore remains standard-of-care for most but new insights into the molecular biology of these diseases, and the development of active targeted molecules offers promise for the future. Accumulating evidence in the very elderly suggests dose attenuation does not compromise survival. Intensification in primary mediastinal B cell lymphoma may avoid the need for radiotherapy, but must be balanced against the risks. PET-CT- and ctDNA-based response assessment may now enable response adapted therapy and early prognostication, improving patient selection and potentially outcomes. Summary Novel technologies and therapies in combination with novel molecular diagnostics will likely become the standard-of-care approach for the personalized therapy of DLBCL but need to be proven in well-designed and conducted randomized trials.