Current standards and future directions in treatment of follicular lymphoma

A number of recent studies have shown that the addition of the monoclonal antibody rituximab to chemotherapy produces survival benefits in first-line treatment of patients with follicular lymphoma (FL). Ongoing phase III trials of first-line therapy are comparing rituximab maintenance versus re-treatment following single-agent therapy in patients with a low tumor burden; rituximab maintenance versus observation in patients with a high tumor burden responding to rituximab plus chemotherapy; and rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) versus CHOP plus radioimmunotherapy with tositumomab/¹³¹I-tositumomab in patients with a high tumor burden. A number of strategies are in development to improve treatment of relapsing disease. A variety of new naked monoclonal antibodies, including those with different antigenic specificities from available agents, are being developed and evaluated for activity in relapsing disease and in initial treatment. Promising new agents in relapsing disease include bortezomib, bendamustine, and lenalidomide. A study of weekly bortezomib has shown comparable response rates and less toxicity compared with a twice-weekly regimen when combined with rituximab. Single-agent bendamustine produced remarkably high response rates in heavily pretreated patients with rituximab-refractory disease. While producing a more modest response rate in pretreated patients, lenalidomide offers the advantage of being an oral therapy. Ongoing investigation of novel agents and strategies is likely to bring further improvement to both first-line and subsequent treatments of FL in the foreseeable future.