Low tumor burden follicular lymphoma: The state of the art

Abstract

Follicular lymphoma (FL) is the commonest indolent non‐Hodgkin lymphoma. Most patients present with advanced‐stage and are stratified by the Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria into high or low tumor burden (LTB). Randomized trials in LTB FL demonstrated no overall survival advantage with immediate treatment compared to watchful waiting (WW). This led to the widespread practice of WW and the consideration of LTB FL as a single indolent continuum. However, LTB FL is heterogeneous, common, and understudied. Recent advances have led to renewed interest and a reconsideration of the optimal approach. Long‐term data comparing rituximab to WW have recently been published providing an understanding of the benefits and limitations of each approach. Novel prognostic models have been developed to predict time to treatment to refine patient selection for WW. Advances in molecular biology have led to an improved understanding of FL lymphomagenesis. Circulating tumor DNA is being explored as a potential highly sensitive response assessment tool. These developments have renewed interest in the optimal approach to management. Early intervention trials with novel agents are currently exploring the hypotheses that LTB FL can be cured, altered, or transformation can be prevented in suitable patients. Conversely, WW remains an appropriate option. In this review, we synthesize the evidence underpinning current paradigms for front‐line management decisions. We propose how the field can be advanced to optimize and individualize care for each patient to live longer and better with LTB FL.