{"entity":{"id":"follicular-lymphoma","kind":"indication","name":"Follicular lymphoma","aka":[],"tldr":"Follicular lymphoma is the most common slow-growing lymphoma, defined in about 85% of cases by a BCL2 translocation. Most people live with it for decades, treated only when it causes problems; it can be controlled repeatedly with anti-CD20 antibodies, chemotherapy, bispecifics or CAR-T but rarely cured, and a small share transform into an aggressive lymphoma each year.","summary":"Follicular lymphoma (FL) is an indolent germinal-centre B-cell lymphoma defined by t(14;18) BCL2 overexpression in ~85% and frequent CREBBP, KMT2D and EZH2 mutations. Median survival now exceeds 15-20 years, so the questions are when to treat, how to avoid over-treatment, and how to manage the ~20% who progress within 24 months (POD24) and the 2-3% per year who transform to DLBCL.\n\nAsymptomatic low-burden disease is watched or given rituximab monotherapy; symptomatic or high-burden disease receives anti-CD20 (rituximab or obinutuzumab) with bendamustine, CHOP or CVP, or with lenalidomide (R², RELEVANCE), usually followed by anti-CD20 maintenance (PRIMA). Relapsed disease has the richest menu in lymphoma: lenalidomide-rituximab (AUGMENT), CD20×CD3 bispecifics (mosunetuzumab 2022, epcoritamab 2024, odronextamab EU), CD19 CAR-T (axicabtagene 2021, tisagenlecleucel 2022, lisocabtagene 2024), zanubrutinib-obinutuzumab (ROSEWOOD, 2024) and radioimmunotherapy historically. Tazemetostat (EZH2) was withdrawn worldwide in March 2026.\n\nOpen questions: whether bispecifics or CAR-T should move to second line or even first line (EPCORE FL-1, MorningSun), PET/ctDNA-guided de-escalation, and biology-based prediction of POD24 and transformation.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Follicular_lymphoma","links":[{"label":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"},{"label":"NCI PDQ: adult NHL","url":"https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq"},{"label":"Lymphoma Research Foundation: FL","url":"https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/fl/"}],"tags":["gap-fill","haematologic"],"related":["dlbcl"],"indications":[],"sections":[],"technologies":["pet-ct","radioimmunotherapy"],"targets":["cd20"],"drugs":["rituximab","ibritumomab-tiuxetan"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"Follicular lymphoma is the second most common non-Hodgkin lymphoma in the West (~20% of NHL; about 3-4 per 100,000 per year), median age ~65.","subtypes":["Classic FL (grades 1-3A)","Follicular large B-cell lymphoma (formerly 3B)","FL with unusual cytological features","Duodenal-type FL","Paediatric-type FL","Transformed FL"],"biomarkers":["t(14;18)/BCL2","FLIPI / FLIPI2 / m7-FLIPI","PET-CT (Lugano) staging and end-of-induction response","POD24 (progression within 24 months)","EZH2 mutation","ctDNA (investigational MRD)"],"standardOfCare":[{"setting":"Limited stage (I-II)","approach":"Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.","refs":["rituximab"],"guideline":{"nccn":"Category 1 (ISRT)","version":"NCCN Guidelines: B-Cell Lymphomas","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480"}},{"setting":"Advanced, low burden, asymptomatic","approach":"Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy.","refs":["rituximab"]},{"setting":"Advanced, high burden (GELF criteria)","approach":"Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA).","refs":["rituximab"],"guideline":{"nccn":"Category 1","esmoMcbs":"3 (GALLIUM)","version":"NCCN Guidelines: B-Cell Lymphomas"}},{"setting":"Relapsed (≥2 lines)","approach":"Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials.","refs":[],"guideline":{"nccn":"Category 2A","version":"NCCN Guidelines: B-Cell Lymphomas"}}],"stateOfArt":["Chemotherapy-free options now exist at every line: R² first line, bispecifics and BTK-anti-CD20 combinations at relapse.","CAR-T gives durable remissions in heavily pretreated FL (ZUMA-5 ~50% progression-free at 4 years) and is being tested against bispecifics.","POD24 identifies the high-risk fifth; how to treat them differently up front is still unknown.","Trials of bispecific plus lenalidomide first line (EPCORE FL-2, CELESTIMO) will decide whether chemotherapy leaves front-line FL."],"history":[{"year":1984,"title":"t(14;18) links BCL2 to follicular lymphoma","note":"Tsujimoto and Croce clone the breakpoint; BCL2 becomes the first anti-apoptotic oncogene.","refs":[]},{"year":1997,"title":"Rituximab approved","note":"First monoclonal antibody for cancer, in relapsed indolent lymphoma.","refs":["rituximab"]},{"year":2004,"title":"FLIPI prognostic index","refs":[]},{"year":2011,"title":"PRIMA: rituximab maintenance","note":"Two years of maintenance doubles PFS after chemo-immunotherapy.","refs":["rituximab"]},{"year":2017,"title":"Obinutuzumab first line (GALLIUM)","refs":[]},{"year":2018,"title":"RELEVANCE: chemo-free R²","note":"Lenalidomide-rituximab matches chemo-immunotherapy first line.","refs":[]},{"year":2021,"title":"CAR-T enters FL","note":"Axicabtagene (ZUMA-5) approved; tisagenlecleucel (ELARA) 2022; lisocabtagene 2024.","refs":[]},{"year":2022,"title":"First bispecific: mosunetuzumab","note":"Off-the-shelf CD20×CD3 with ~60% CR in third line.","refs":[]},{"year":2024,"title":"Epcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL","refs":[]},{"year":2026,"title":"Tazemetostat withdrawn worldwide","note":"Secondary haematologic malignancies; EZH2 leaves the FL armamentarium.","refs":[]}],"pipeline":[],"openProblems":["Transformation to DLBCL cannot be predicted or prevented.","Sequencing bispecifics vs CAR-T.","Whether earlier intensive therapy for POD24 patients improves survival.","Late toxicities of decades of therapy (secondary cancers, infections, immunoglobulin loss)."]},"route":"/indications/follicular-lymphoma/","neighbours":{"indication":[{"id":"dlbcl","kind":"indication","name":"Diffuse large B-cell lymphoma","route":"/indications/dlbcl/"}],"technology":[{"id":"pet-ct","kind":"technology","name":"PET/CT","route":"/technologies/pet-ct/"},{"id":"radioimmunotherapy","kind":"technology","name":"Radio-antibody & radio-ADC","route":"/technologies/radioimmunotherapy/"}],"target":[{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"}],"drug":[{"id":"ibritumomab-tiuxetan","kind":"drug","name":"Ibritumomab tiuxetan","route":"/drugs/ibritumomab-tiuxetan/"},{"id":"i-131-tositumomab","kind":"drug","name":"Iodine-131 tositumomab","route":"/drugs/i-131-tositumomab/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}],"company":[{"id":"acrotech-biopharma","kind":"company","name":"Acrotech Biopharma","route":"/companies/acrotech-biopharma/"}],"pairing":[{"id":"rituximab-then-ibritumomab-tiuxetan","kind":"pairing","name":"Rituximab pretreatment before ibritumomab tiuxetan (Zevalin)","route":"/pairings/rituximab-then-ibritumomab-tiuxetan/"}]}}