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Follicular lymphoma

Abstract

Follicular lymphoma (FL) is a systemic neoplasm of the lymphoid tissue displaying germinal centre (GC) B cell differentiation. FL represents ~5% of all haematological neoplasms and ~20–25% of all new non-Hodgkin lymphoma diagnoses in western countries. Tumorigenesis starts in precursor B cells and becomes full-blown tumour when the cells reach the GC maturation step. FL is preceded by an asymptomatic preclinical phase in which premalignant B cells carrying a t(14;18) chromosomal translocation accumulate additional genetic alterations, although not all of these cells progress to the tumour phase. FL is an indolent lymphoma with largely favourable outcomes, although a fraction of patients is at risk of disease progression and adverse outcomes. Outcomes for FL in the rituximab era are encouraging, with ~80% of patients having an overall survival of >10 years. Patients with relapsed FL have a wide range of treatment options, including several chemoimmunotherapy regimens, phosphoinositide 3-kinase inhibitors, and lenalidomide plus rituximab. Promising new treatment approaches include epigenetic therapeutics and immune approaches such as chimeric antigen receptor T cell therapy. The identification of patients at high risk who require alternative therapies to the current standard of care is a growing need that will help direct clinical trial research. This Primer discusses the epidemiology of FL, its molecular and cellular pathogenesis and its diagnosis, classification and treatment.

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Fig. 1: Origin of mature B cell lymphomas.
Fig. 2: A model for the stepwise evolution of FL.
Fig. 3: The FL tumour microenvironment.
Fig. 4: Cellular features of the germinal centre in health and disease.
Fig. 5: Immunophenotype of follicular lymphoma.
Fig. 6: In situ follicular neoplasia.
Fig. 7: Standard first-line therapy of follicular lymphoma.

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Acknowledgements

The authors thank V. Matarese (Centro di Riferimento Oncologico di Aviano) for scientific editing of an early draft of the “Mechanisms/pathophysiology” and “Diagnosis, screening and prevention” sections, and Tables 1 and 2, Box 1 and Fig. 1. A.G. is supported in part by the Italian Ministry of Health (5×1000 Funds–2015), through institutional grant BRI2018 ‘Progetto 6 — visualizing immunomodulatory molecules in individual human cancer cells using in situ bright field multiplexing methods and an innovative proximity detection assay’. S.R. is supported by the Fondation ARC, Cancéropôle Provence-Alpes-Côte d’Azur, the Institut National du Cancer, and by institutional grants from INSERM and CNRS.

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Introduction (A.C.); Epidemiology (S.R.); Mechanisms/pathophysiology (A.G. and S.R.); Diagnosis, screening and prevention (A.C., A.G. and S.R.); Management (A.Y. and G.v.K.); Quality of life (A.L.-G.); Outlook (J.F.); Overview of Primer (A.C.).

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Correspondence to Antonino Carbone.

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Competing interests

A.Y. receives research support from BMS, Curis, Janssen, Merck, Roche and Syndax; honoraria from Abbvie, Curis, Epizyme, Janssen, Merck, Roche and Takeda; and has a consulting role for Biopath, Celgene, Epizyme, HCM, Roche and Xynomics. G.v.K. receives honoraria from Pharmacyclics and has a consulting or advisory role for Bayer, Genentech and Pharmacyclics. A.L.-G. receives research funding from Roche and Gilead and has an advisory role for Bayer, Gilead, Janssen, Novartis, Pfizer (not personal fees) and Roche. J.F. receives research funding from Epizyme and honoraria from Gilead and Roche. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks W. Hiddemann, L. Nastoupil, K. Tarte and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Carbone, A., Roulland, S., Gloghini, A. et al. Follicular lymphoma. Nat Rev Dis Primers 5, 83 (2019). https://doi.org/10.1038/s41572-019-0132-x

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