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Teaching pack: Follicular lymphoma

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9 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.

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  1. Teaching pack · Cancer · haematologic

    Follicular lymphoma

    Follicular lymphoma is the most common slow-growing lymphoma. Most people live many years with it, treated only when it causes problems; it can be controlled repeatedly but rarely cured, and a minority transform into an aggressive lymphoma.

    Teaching pack: Follicular lymphoma · OnCo, CC BY 4.0 · not medical advice1 / 9
  2. What it is

    In two paragraphs

    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 Tazemetostat (EZH2) was withdrawn worldwide in March 2026.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Limited stage (I-II)Involved-site radiotherapy 24 Gy (FoRT); rituximab alone or observation in selected cases.NCCN Category 1 (ISRT)
    Advanced, low burden, asymptomaticWatch 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
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  4. State of the art

    Where the field stands

    • 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.
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  5. History

    How we got here

    1. 1984t(14;18) links BCL2 to follicular lymphoma
    2. 1997Rituximab approved
    3. 2004FLIPI prognostic index
    4. 2011PRIMA: rituximab maintenance
    5. 2017Obinutuzumab first line (GALLIUM)
    6. 2018RELEVANCE: chemo-free R²
    7. 2021CAR-T enters FL
    8. 2022First bispecific: mosunetuzumab
    9. 2024Epcoritamab and zanubrutinib-obinutuzumab approved for relapsed FL
    10. 2026Tazemetostat withdrawn worldwide
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  6. Pipeline

    What is coming

    • Epcoritamab (product)
    • Mosunetuzumab (product)
    • Odronextamab (product)
    • Golcadomide (product)
    • Lisocabtagene maraleucel (product)
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  7. Open problems

    What nobody has solved

    • 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).
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  8. Quiz

    Check understanding

    1. How did CAR-T change second-line treatment of large B-cell lymphoma?
      Answer
      ZUMA-7 showed axicabtagene ciloleucel beats standard chemotherapy plus transplant for early relapse; CAR-T is now second-line standard, curing around 40% of relapsed patients.
    2. Why does venetoclax work in leukaemia?
      Answer
      It blocks BCL-2, the protein that stops leukaemia cells from self-destructing, so the built-in death programme (apoptosis) can run; used in CLL (fixed duration with obinutuzumab) and AML (with azacitidine).
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  9. Sources

    Read the primary sources

    • NCCN Guidelines: B-Cell Lymphomas: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480
    • NCI PDQ: adult NHL: https://www.cancer.gov/types/lymphoma/patient/adult-nhl-treatment-pdq
    • Lymphoma Research Foundation: FL: https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/fl/
    • Wikipedia: https://en.wikipedia.org/wiki/Follicular_lymphoma
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480
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