Follicular lymphoma
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.
Overview
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.
Asymptomatic 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 Tazemetostat (EZH2) was withdrawn worldwide in March 2026.
Open 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.
State of the art
- 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.
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
- Bone marrow (leukaemia, MDS, MPN, myeloma)Follicular large B-cell lymphoma (formerly 3B)
- Lymph node germinal centre (lymphomas)Follicular large B-cell lymphoma (formerly 3B) · Transformed FL
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: Diffuse large B-cell lymphoma
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.
Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.
Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy.
Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA).
Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials.
Subtypes & biomarkers
top- 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
- 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)
How often this target appears
- 1984t(14;18) links BCL2 to follicular lymphoma
Tsujimoto and Croce clone the breakpoint; BCL2 becomes the first anti-apoptotic oncogene.
- 1997Rituximab approved
First monoclonal antibody for cancer, in relapsed indolent lymphoma.
- 2004FLIPI prognostic index
- 2011PRIMA: rituximab maintenance
Two years of maintenance doubles PFS after chemo-immunotherapy.
- 2017Obinutuzumab first line (GALLIUM)
- 2018RELEVANCE: chemo-free R²
Lenalidomide-rituximab matches chemo-immunotherapy first line.
- 2021CAR-T enters FL
Axicabtagene (ZUMA-5) approved; tisagenlecleucel (ELARA) 2022; lisocabtagene 2024.
- 2022First bispecific: mosunetuzumab
Off-the-shelf CD20×CD3 with ~60% CR in third line.
- 2024Epcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL
- 2026Tazemetostat withdrawn worldwide
Secondary haematologic malignancies; EZH2 leaves the FL armamentarium.
Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 19 changes by month →- 2026-09-08This recordFollicular lymphomaFacts on this page last checked
When this page itself was last checked or edited.
- 2026MilestoneFollicular lymphomaTazemetostat withdrawn worldwide
Secondary haematologic malignancies; EZH2 leaves the FL armamentarium.
- 2024MilestoneFollicular lymphomaEpcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL
A milestone in how this cancer is treated.
- 2022MilestoneFollicular lymphomaFirst bispecific: mosunetuzumab
Off-the-shelf CD20×CD3 with ~60% CR in third line.
- 2021MilestoneFollicular lymphomaCAR-T enters FL
Axicabtagene (ZUMA-5) approved; tisagenlecleucel (ELARA) 2022; lisocabtagene 2024.
- 2018MilestoneFollicular lymphomaRELEVANCE: chemo-free R²
Lenalidomide-rituximab matches chemo-immunotherapy first line.
What is in development for Follicular lymphoma, drawn from the whole corpus: 2 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Technologies being tested · 1
Combinations being explored · 1
Open problems and what is being done
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).
Trials
topTrials recruiting now
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Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
2targets
1drugs
3companies
1pairings
1Latest papers
topQuery for this indication: (TITLE:"Follicular lymphoma" OR ABSTRACT:"Follicular lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Follicular lymphoma, not a curated reading list.
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