Frontline therapy with R-CHOP for diffuse large B-cell lymphoma: Where have we come (or not come)? A Perspective.

A major evolution in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) occurred almost two decades ago, with clinical trials demonstrating that the addition of rituximab (R) to cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), which had been the "gold standard" of therapy since 1976, significantly improved outcome, including response rate and disease-free survival, of these patients. Since the adoption of R-CHOP, subsequent clinical trials have attempted to improve upon outcomes achieved with R-CHOP, with a variety of approaches examined. These have included dose intensification, which may be applicable in younger patients, but not in the many older or frailer patients with a disease with median age at diagnosis in the 60's. Newer anti-CD20 monoclonal antibodies have been substituted for rituximab in frontline regimens. A series of new agents, with unique mechanisms of action, have been added to the R-CHOP backbone. Rituximab-based, non-anthracycline regimens have been studied for older, more frail patients. The utility of maintenance therapy in responding patients has been re-examined, despite the lack of benefit found in the US Intergroup trial. Advances in molecular and genetic aspects of DLBCL have emerged since the seminal R-CHOP trials, demonstrating the DLBCL is not a single entity, but instead a spectrum of multiple disease subtypes. Attempts have been made to identify those patients at baseline who have poorer outcomes with standard approaches, utilizing laboratory and imaging findings. Moving forward, different risk-adapted treatment approaches will be studied to in an effort to improve overall outcome beyond R-CHOP.