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Follicular lymphoma (FL) is an indolent lymphoid neoplasm derived from germinal center B cells. It is the most frequent indolent non-Hodgkin lymphoma, accounting for about 20% of all cases. FL is characterized by the t(14;18) (q32;q21) occurring early in the B-cell differentiation process at the pre-B cell stage and leading to the overexpression of the antiapoptotic protein BCL2. However, this translocation, present in circulating B cells at a very low level in up to 70% of healthy individuals, is a weak oncogenic driver, and FL is a multistep disease, requiring additional genomic abnormalities to develop the fully malignant phenotype. The disease is highly “subclonal” at diagnosis, as shown by the variability in allele frequency of the recurrent oncogenic events affecting not only the epigenetic immune escape but also the B-cell receptor, mTOR (mammalian target of rapamycin) and prosurvival pathways. The biological heterogeneity of FL results in a variable clinical presentation and evolution, ranging from a very indolent disease that can be managed for many years with a “watch and wait” approach to an aggressive transformation into diffuse large B-cell lymphoma (DLBCL) and shortened overall survival. When treatment is needed, the use of a monoclonal antibody against CD20 combined with chemotherapy allows a survival of nearly 80% at 10 years. Several prognostic indices based on clinical, biological, and genetic parameters have been developed and validated, but the strongest prognostic factor is the occurrence of an early relapse after treatment initiation (ie, within 24 months). These early events tend to be associated with a histologic transformation (HT) to DLBCL and a very poor outcome. Despite improvements in the genomic characterization of the disease, the accurate prediction of HT at the time of FL diagnosis remains elusive. A better understanding of the interaction between the immune microenvironment and tumor cells may allow the development of targeted therapies and chemotherapy-free options for patients with FL.

Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from germinal center (GC) B cells and has a nodular or follicular histologic pattern. In view of the indolent nature of this type of lymphoma, a rapid therapeutic decision is rarely required. Furthermore, this indolence means that treatment only needs to be offered to patients with symptomatic disease. The use of a monoclonal antibody against CD20 (rituximab, obinutuzumab) combined with chemotherapy allows a survival of nearly 80% at 10 years. Therefore, because of the frequently advanced age of the patient at diagnosis and the disease’s indolence, although the disease is still considered largely incurable, some patients will never need to receive treatment. Furthermore, among those who require treatment, most will not see their disease relapse or die from their disease, even though FL remains the major cause of death in these patients. Indeed, the challenge today is to identify patients who need treatment and then define the most appropriate treatment for them considering their age, comorbidities, and likelihood of relapse. Fewer than 20% of patients receiving ...

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