What is the best first-line treatment strategy for patients with indolent lymphomas?

Although advanced follicular lymphoma is considered incurable, patient outcomes have improved over the last decade with the use of anti-CD20 monoclonal antibodies. Multiple treatment options are available and their use depends on clinical presentation (i.e., Ann Arbor stage, tumor burden, symptoms) and patient condition and age. Radiation therapy for patients with limited stage disease remains useful, although its use in the era of anti-CD20 antibodies should be re-evaluated. Single-agent rituximab has been tested in multiple studies with patients with low tumor burden. Short treatment duration provides a response lasting 2 to 3 years, although the benefit of maintenance therapy with rituximab after induction therapy with rituximab remains unproven. When watchful waiting is not an option, a combination of rituximab with chemotherapy is the standard of care: alkylating agents with anthracycline or bendamustine appear to be the most widely used regimens, but alkylating agents alone may still be used in selected patients subgroups. The toxicity of regimens containing fludarabine appears to limit their indication as first-line treatment. In patients responding to one of these combinations, consolidation therapy with rituximab maintenance has been shown to prolong progression-free survival with acceptable toxicity. The benefit of radioimmunotherapy in first-line treatment is still uncertain. With patients surviving for many years, the therapeutic strategy of first-line management should weigh the quality and duration of response against the risk of long-term toxicities.