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10 standard-of-care settings across 7 lines and 1 biomarker subgroup. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.
| Line | All comers |
|---|---|
| Early / localised | 1 |
| Locally advanced | 1 |
| Advanced, first line | 3 |
| Maintenance | 1 |
| Second line | 2 |
| Third line and beyond | 1 |
| Other settings | 1 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | 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. | FoRT: 4 Gy versus 24 Gy radiotherapy for indolent lymphoma, a randomised phase 3 non-inferiority trialRadiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapyIMRT / IGRT (modern external beam)FDG PETRituximabCyclophosphamideVincristinePrednisoneWatch and wait in lymphoma: when the right treatment is none yetFLIPI, FLIPI2 and POD24 (follicular lymphoma risk) | NCCN B-Cell Lymphomas; ESMO; TROG 99.03, FoRT | 93 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Limited stage (I-II) | Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases. | NCCN · Category 1 (ISRT) | 93 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Advanced, low burden, asymptomatic | Watch and wait (no survival penalty), or rituximab monotherapy to delay chemotherapy. | 84 | ||
| All comers | 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 1ESMO-MCBS · 3 (GALLIUM) | 91 | |
| All comers | 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 burd… | 84 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | 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. | GALLIUMRELEVANCEObinutuzumabRituximabBendamustineLenalidomideR-CHOP (lymphoma chemoimmunotherapy)CyclophosphamideVincristinePrednisoneMaintenance and consolidation in lymphoma: where it works and where it does notBendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trialGALLIUM: obinutuzumab for the first-line treatment of follicular lymphomaRELEVANCE: rituximab plus lenalidomide in advanced untreated follicular lymphoma | NCCN · Category 1 | 91 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | 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 | 83 | |
| All comers | 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. | POD24: progression of follicular lymphoma within two years, and why it changes the planZUMA-5Axicabtagene ciloleucelTisagenlecleucelMosunetuzumabOdronextamabEpcoritamabLenalidomideRituximabCAR-T cell therapyThe CAR-T pathway in lymphoma: referral, apheresis, bridging and the waitingAutologous stem cell transplant (high-dose therapy)FLIPI, FLIPI2 and POD24 (follicular lymphoma risk) | NCCN B-Cell Lymphomas; ESMO; ZUMA-5, ELARA | 91 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Relapsed follicular lymphoma after two or more lines: bispecific antibodies, CAR-T and R-squared | Nothing here is curative and all of it can produce long remissions, so the choice is about duration of treatment, side effects and how far a person is willing to travel. Fixed-duration bispecific antibodies. Mosunetuzumab, given intravenously in 21-day cycles with step-up dosing and stopped after eight cycles in complete responders, produced a complete response in 60.0 per cent of 90 patients after two or more lines. Odronextamab in ELM-2 gave an objective response of 80.0 per cent, complete response 73.4 per cent and median progression-free survival 20.7 months in 128 patients, with grade 3 or worse cytokine release syndrome of 1.7 per cent using the split step-up. Epcoritamab is approved in combination with rituximab and lenalidomide. CAR-T. Axicabtagene ciloleucel (ZUMA-5) and tisagenlecleucel (ELARA) both produce high complete response rates with remissions that are lasting in a substantial minority; the trade is a single intensive episode against repeated outpatient treatment. Rituximab with lenalidomide. AUGMENT randomised 358 patients with relapsed follicular or marginal zone lymphoma to lenalidomide with rituximab or rituximab with placebo: median progression-free survival 39.4 against 14.1 months (hazard ratio 0.46), with grade 3 to 4 neutropenia in 50 against 13 per cent. Antibody and inhibitor combinations approved since 2024. Tafasitamab with lenalidomide and rituximab received traditional United States approval on 18 June 2025 on the inMIND trial, with a label note that it is not indicated in relapsed or refractory marginal zone lymphoma outside a trial. Zanubrutinib with obinutuzumab was given accelerated approval on 7 March 2024 on ROSEWOOD. Lisocabtagene maraleucel's follicular approval of 15 May 2024 converted to traditional approval on 20 February 2026, and a separate marginal zone lymphoma approval followed on 4 December 2025. Other options: a different chemoimmunotherapy backbone from the one used before, obinutuzumab with bendamustine in rituximab-refractory disease, tazemetostat for EZH2-mutant disease or where nothing else is suitable, radiotherapy to a single symptomatic site, and radioimmunotherapy where it is still available. The PI3K inhibitors (idelalisib, duvelisib, copanlisib) have largely been withdrawn from this indication on the basis of toxicity and unconfirmed benefit. | AUGMENTZUMA-5MosunetuzumabOdronextamabEpcoritamabLenalidomideRituximabObinutuzumabBendamustineTazemetostatAxicabtagene ciloleucelTisagenlecleucelLisocabtagene maraleucelTafasitamabZanubrutinibRadio-antibody & radio-ADCCD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take oneRadiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapyAUGMENT: lenalidomide plus rituximab versus rituximab alone in relapsed indolent lymphoma | NCCN B-Cell Lymphomas; ESMO; AUGMENT, ELM-2, mosunetuzumab phase 2 | 91 |
| Subgroup | Setting | Approach | Products and trials | Guideline | Evidence |
|---|---|---|---|---|---|
| All comers | Transformation of follicular lymphoma to diffuse large B-cell lymphoma | Suspected when a single site grows quickly, LDH rises, B symptoms appear or the PET shows one site far brighter than the rest; confirmed by biopsy of that site, which is why a repeat biopsy rather than a scan is the right first step. It occurs in roughly 2 to 3 per cent of patients a year. Treatment follows the aggressive lymphoma pathway, not the follicular one. In a patient who has had little or no previous chemotherapy, R-CHOP or pola-R-CHP with the intent to cure, often followed by consideration of autologous transplant consolidation. In a patient who has already had several lines, CD19 CAR-T; transformed disease was included in the pivotal CAR-T populations. Bispecific antibodies are active. The outlook is better than it was when transformation was treated with more of the same. | R-CHOP (lymphoma chemoimmunotherapy)POLARIXPolatuzumab vedotinRituximabAxicabtagene ciloleucelLisocabtagene maraleucelGlofitamabEpcoritamabAutologous stem cell transplant (high-dose therapy)FDG PETThe CAR-T pathway in lymphoma: referral, apheresis, bridging and the waitingPOD24: progression of follicular lymphoma within two years, and why it changes the plan | NCCN B-Cell Lymphomas; ESMO | 89 |
Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.