Advanced-stage follicular lymphoma in the rituximab era: when should patients receive anthracycline-based chemotherapy?

Follicular lymphoma (FL), the most common subtype of indolent lymphoma, is usually diagnosed at an advanced stage (III-IV), although patients are often asymptomatic. Traditionally, a palliative approach to management has been taken, cycling through watchful waiting, radiotherapy, oral alkylating agents and, eventually, combination chemotherapy, as deemed necessary. However, accumulating evidence suggests that in patients requiring treatment, early initiation of an anthracycline-based regimen may achieve better response rates and progression-free survival compared with reserving such options until late in the course of disease. Delivery of myelosuppressive chemotherapy has been facilitated by the availability of granulocyte colony-stimulating factors. Incorporation of the anti-CD20 monoclonal antibody rituximab into upfront chemotherapy regimens further improves outcomes. With a trend towards early use of rituximab chemotherapy combinations, median survival appears to have increased in patients with FL. A number of issues remain to be addressed by ongoing research. These include identification of the most effective rituximab chemotherapy regimen, the impact of treatment on responsiveness to future treatment, the need for rituximab maintenance therapy and the place of newer treatments. Clearly, there are arguments in favour of considering early aggressive rituximab and chemotherapy regimens in patients with FL requiring treatment, and it is hoped that new prognostic tools will help us to more accurately identify which patients are most likely to benefit.