DIffuse large B-cell lymphoma

Cummin, Thomas (2016) DIffuse large B-cell lymphoma. In, Copson, Ellen R., Hall, Peter, Board, Ruth, Cook, Gordon and Selby, Peter (eds.) Problem Solving in Precision Oncology. pp. 45-51.

Abstract

Diffuse large B cell lymphoma (DLBCL) is the commonest aggressive non-Hodgkin’s lymphoma, accounting for approximately 4200 new cases annually in the UK.1 Standard of care rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP) achieves cure in approximately 60% of cases.2 Patients who remain refractory or relapse have a poor outlook: around 20% event-free survival is recorded at 3 years.3 Attempts to intensify chemotherapy for high-risk subgroups have so far been unable to clearly recommend an improved, widely adopted approach. Recent advances surrounding molecular diagnostics reveal a heterogeneous disease that provides potential therapeutic targets to improve outcomes. DLBCL will likely require a personalized medicine approach to improve responses and survival for patients. Intensified
chemotherapy regimens for high-risk subgroups, checkpoint inhibitors, monoclonal antibodies and small molecule agents represent opportunities to investigate and subsequently widen the armamentarium against DLBCL. Identification of predictive biomarkers to direct therapy will be necessary to unpick the complexity of this disease and guide subgroups towards precision therapy.
Traditionally, DLBCL has been diagnosed by light microscopy and immunostaining of lymphoma tissue. Recent advances in molecular diagnostics have revealed marked heterogeneity and distinct subtypes. Through better characterization it is hoped that researchers can understand which features better confer immunochemotherapy resistance and identify targets for novel
treatments. Gene expression profiling has revealed at least three distinct subtypes that represent clinically and biologically distinct entities.4 Potential targets of recurrent somatic point mutations have been identified through application of genome, exome and RNA sequencing, and more than 200 mutations have been found.

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