Second-line treatment paradigms for diffuse large B-cell lymphomas

Despite recent major advances in treating diffuse large B-cell lymphoma with dose-intense regimens and the addition of the anti-CD20 monoclonal antibody rituximab, a significant proportion of patients will experience early treatment failure, partial response, or relapse after initial chemotherapy. For more than 10 years, the standard treatment for chemosensitive relapses has been based on salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation in selected patients. However, several important questions remain: What is the best salvage regimen? What is the efficacy of rituximab in an era when R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is accepted as standard care for frontline therapy? What are the risk factors in second-line therapy? What is the best treatment when high-dose therapy and autologous stem cell transplantation are not possible? This article reviews all these issues and discusses new biologic therapies, with the knowledge that improvements in outcome may be achieved through a greater understanding of the biologic parameters associated with poorer prognosis.