Paramount prognostic factors that guide therapeutic strategies in diffuse large B-cell lymphoma.

Outcome in diffuse large B-cell lymphoma (DLBCL) has improved over the last decade and will likely improve further with the introduction of novel agents. At the present time, clinical prognostic factors are limited in their ability to identify patients with sufficiently poor outcome to justify deviation of therapy away from R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) outside of a clinical trial. Similarly, with the exception of the concurrent translocation of MYC and BCL2, there are no validated biologic markers that can be used to guide initial therapy in routine practice. Recognition of the molecular heterogeneity of DLBCL is of paramount importance and must be taken into consideration when investigating new therapies. It will be vital for novel targeted agents to be evaluated in patient populations enriched for those who are most likely to benefit. The identification of prognostic and predictive biomarkers should be initiated during the early phase of drug development so that these tests can be validated within phase 3 trials. Although currently available techniques such as immunohistochemistry may still be used, gene-expression profiling and whole genomic analytic techniques will likely play a major role in the evaluation of patients in the future to determine optimal personalized treatment for DLBCL.