Optimizing initial therapy in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is a group of lymphomas comprising heterogeneous molecular and biological subtypes, reflected in a broad range of clinical outcomes. With the standard R-CHOP regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab administered every 21 days, the treatment failure rate remains unacceptably high in certain DLBCL subsets. Here we review possible avenues for optimizing initial therapy. The role of functional imaging and biological features, such as double-hit lymphomas, defined by the dual translocation of MYC and BCL2, and dual protein-expresser lymphomas, defined by the overexpression of MYC and BCL2, activated B-cell (ABC)-like DLBCL, to better define these high-risk patient subsets, and their use to guide and personalize treatment decisions are discussed. Secondly, the implications of varying dose-intensification of the various agents administered, and the link to imaging are reviewed. Thirdly, the results of the addition of novel drugs to standard R-CHOP will be analyzed, when added at induction or in maintenance. Finally, with CNS relapse in DLBCL representing a major and devastating unmet medical need, an overview and future directions for CNS prophylaxis is presented.