Controversies in follicular lymphoma: "who, what, when, where, and why?" (not necessarily in that order!)

Follicular lymphoma (FL) is the most common subtype of indolent lymphoma. Specific "facts" about FL that were generated by past research and have been passed down as dogma to a majority of practicing oncologists over the past 20 to 30 years that need to be revisited, include: (1) do not initiate therapy soon after diagnosis in asymptomatic, advanced-stage patients since it does not change outcome; (2) initiate therapy with single-agent oral alkylators when intervention needed and "save" more aggressive combination chemotherapy for "later" since the standard chemotherapy regimen used did not seem to impact survival; (3) FL is an incurable disease and palliation of symptoms was an acceptable approach to the expected pattern of repeated relapses; (4) transformation of FL is independent of the type or timing of therapies received by a patient; (5) median overall survival (OS) for FL patients is 8-10 years. Although the heterogeneity of FL will never change, we are developing the scientific tools to identify and better understand the biologic and genetic features associated with its clinical variability. In the current exciting era of targeted therapies (e.g., rituximab, radioimmunoconjugates) and novel treatment approaches demonstrating an improvement in treatment outcomes (e.g., disease-free survival and OS), our old beliefs and historically accepted dogma need to be retested and revitalized. The optimal combination(s) of old and new agents and the optimal timing of when to initiate and how to sequence specific therapies will require data from well-designed clinical trials that should include important correlative laboratory studies.