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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
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.
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 Tazemetostat (EZH2) was withdrawn worldwide in March 2026.
| Setting | Approach | Guideline |
|---|---|---|
| Limited stage (I-II) | Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases. | NCCN Category 1 (ISRT) |
| Advanced, low burden, asymptomatic | Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy. | not mapped |
| Advanced, high burden (GELF criteria) | Bendamustine-rituximab or bendamustine-obinutuzumab (GALLIUM), R-CHOP, or lenalidomide-rituximab (RELEVANCE); anti-CD20 maintenance 2 years (PRIMA). | NCCN Category 1, ESMO-MCBS 3 (GALLIUM) |
| Relapsed (≥2 lines) | Lenalidomide-rituximab (AUGMENT); CD20×CD3 bispecific (mosunetuzumab, epcoritamab); CD19 CAR-T (axi-cel, tisa-cel, liso-cel); zanubrutinib + obinutuzumab; clinical trials. | NCCN Category 2A |
| Stage I and contiguous stage II follicular lymphoma: radiotherapy with curative intent | Truly localised follicular lymphoma, which means stage I or contiguous stage II confirmed on PET-CT and marrow assessment, is treated with 24 Gy in 12 fractions to an involved-site field and a substantial minority never relapse. PET staging matters: a quarter or more of patients thought to have stage I on CT are upstaged, and those are the ones who relapse outside the field. Adding systemic treatment lengthens remission without proven survival gain. TROG 99.03 randomised 150 patients after 30 Gy involved-field radiotherapy to observation or six cycles of CVP, with rituximab added from 2006: ten-year progression-free survival was 59 per cent with systemic therapy against 41 per cent with radiotherapy alone (hazard ratio 0.57), overall survival was not significantly different (95 against 87 per cent), and the effect was largest in the rituximab-containing subgroup. Four gray in two fractions is not an alternative for cure: FoRT found it clearly inferior to 24 Gy for local control. Observation is a defensible option in an older patient with a small, asymptomatic node, and so is rituximab alone. Doing nothing is not the same as doing nothing wrong. | not mapped |
| Advanced follicular lymphoma with no symptoms: watch and wait, or rituximab alone | Starting chemotherapy early does not lengthen life in asymptomatic, low-burden disease, and a third of people never need treatment in the first few years. The British-led trial that settled this randomised 379 patients with asymptomatic, non-bulky, advanced disease: at three years, 46 per cent of those watched had not needed treatment against 88 per cent of those given four weekly doses of rituximab and two years of maintenance (hazard ratio 0.21), with no overall survival difference. So rituximab delays the next treatment; it does not extend life, and it costs two years of visits. The GELF criteria are the usual trigger to treat: a mass of 7 cm or more, three or more nodal sites each 3 cm or more, B symptoms, splenomegaly, effusion, cytopenias or a leukaemic phase. Monitoring is clinic review and bloods every three to six months; routine scanning of a well person finds little. | NCCN Category 1 (observation for low tumour burden) |
| Advanced follicular lymphoma needing treatment: which induction, and whether to add maintenance | Chemoimmunotherapy is the usual first treatment, and the choice of chemotherapy backbone is made on toxicity. Bendamustine with rituximab gave median progression-free survival of 69.5 against 31.2 months for R-CHOP in the StiL NHL1 trial of indolent and mantle cell lymphoma (hazard ratio 0.58), with no alopecia, less haematological toxicity, fewer infections and far less neuropathy, and is the commonest first choice; it does deplete T cells for a long time, which matters for anyone who may need CAR-T later. R-CHOP is preferred where transformation is suspected. R-CVP is the gentlest. Obinutuzumab instead of rituximab improves progression-free survival: GALLIUM randomised 1,401 patients and gave three-year progression-free survival of 80.0 against 73.3 per cent (hazard ratio 0.66), at the cost of more grade 3 to 5 adverse events (74.6 against 67.8 per cent) and more infusion reactions. Chemotherapy-free induction is a real alternative. RELEVANCE randomised 1,030 patients to rituximab with lenalidomide or rituximab with the investigator's chemotherapy: complete response at 120 weeks was 48 against 53 per cent and median progression-free survival 120.2 against 123.8 months (hazard ratio 0.92), so R-squared is not superior but is equivalent, with less neutropenia (32 against 50 per cent) and more rash. Maintenance rituximab for two years afterwards lengthens remission substantially and does not lengthen life: in PRIMA median progression-free survival was 10.5 against 4.1 years but ten-year overall survival was about 80 per cent in both arms. It is a choice, not a requirement. | NCCN Category 1 |
| Progression within two years of first chemotherapy (POD24): biopsy first, then a different class of treatment | About one in five people treated with first-line chemoimmunotherapy progress within two years, and their five-year overall survival in the National LymphoCare Study was 50 per cent against 90 per cent for everyone else, a difference that held after adjusting for FLIPI. The first step is a repeat biopsy, because transformation to diffuse large B-cell lymphoma is the commonest explanation and is treated as aggressive lymphoma. If it is still follicular, the plan changes class rather than repeating it: CD19 CAR-T (ZUMA-5 reported an overall response of 92 per cent and complete response 74 per cent; ELARA with tisagenlecleucel reported complete response 69.1 per cent and overall response 86.2 per cent), a CD20 bispecific antibody, or lenalidomide with rituximab. A clinical trial is a reasonable first choice at this point. Autologous transplant still has a role in younger patients with chemosensitive early relapse and is used less than it was. | not mapped |