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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 Tazemetostat (EZH2) was withdrawn worldwide in March 2026.
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.
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.
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.
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: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
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.
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.
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.
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.
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.
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.
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.
Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year.
The targets of this cancer's medicines and the ones linked to it directly.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Lymphoma Action says a small number of people have more serious problems such as seizures or swelling of the brain, treated with steroids and intensive care, and that most improve within a few days of treatment starting. This is 999.
Fever of 38 C or higher, chills, low blood pressure, fast heartbeat or breathlessness, especially after a step-up dose. Boxed warning on teclistamab, epcoritamab, glofitamab, tarlatamab and blinatumomab.
Breathing very fast, confusion or slurred speech, blue, pale or blotchy skin, a very high or very low temperature, shivering, or a rash that does not fade when pressed: the NHS says call 999 or go to A and E, and do not drive yourself.
Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fever of 38 C or higher is grade 1 CRS; fever with low blood pressure, fast heartbeat, breathlessness or low oxygen is grade 2 or higher. The labels carry a boxed warning and say to report fever immediately.
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
See all on the product pages:Axicabtagene ciloleucelBendamustineCD20 bispecific antibodies: step-up dosing, fixed duration and what it is like to take oneCentral venous access (port, PICC line)CyclophosphamideCytokine release syndrome (CRS)Cytokine release syndrome and ICANS: grading and managementEpcoritamabFebrile neutropeniaGlofitamabHypogammaglobulinaemia and infection risk after B-cell therapiesICANS (neurotoxicity)LenalidomideLisocabtagene maraleucelMosunetuzumabNeutropeniaOdronextamabThe CAR-T pathway in lymphoma: referral, apheresis, bridging and the waitingTisagenlecleucelVincristine·Printable cards in the navigator
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