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Teaching pack: Mantle cell 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

    Mantle cell lymphoma

    An uncommon B-cell lymphoma driven by cyclin D1 that used to behave badly in almost everyone. BTK inhibitors, CAR-T and now BCL2 drugs have changed it from chemotherapy-plus-transplant to targeted combinations.

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  2. What it is

    In two paragraphs

    Mantle cell lymphoma (MCL) carries t(11;14) with cyclin D1 overexpression (SOX11-positive in classical MCL). Risk is set by MIPI, Ki-67, blastoid morphology and TP53 mutation, the last defining a group that fails chemo-immunotherapy and transplant. A leukaemic non-nodal variant behaves indolently.

    Younger fit patients traditionally received cytarabine-containing induction and autologous transplant with rituximab maintenance; TRIANGLE (2024) showed adding ibrutinib to induction and maintenance is at least as good as transplant, and transplant is being abandoned. Older patients receive bendamustine-rituximab or R-CHOP; ECHO (2024) added acalabrutinib to BR first line (FDA approval 2025). Relapse is treated with covalent BTK inhibitors (ibrutinib 2013, acalabrutinib 2017, zanubrutinib 2019; ibrutinib's US MCL approval was withdrawn in 2023 after SHINE), then brexucabtagene autoleucel (ZUMA-2, 2020), the non-covalent BTKi pirtobrutinib (2023), or the BCL2 inhibitor sonrotoclax (2026); venetoclax-ibrutinib (SYMPATICO) is another option. Lisocabtagene was approved for MCL in 2024.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    First line, fit (<65-70)Rituximab + high-dose cytarabine-based induction (e.g. R-CHOP/R-DHAP or Nordic) with ibrutinib and 2 years ibrutinib maintenance; autologous transplant no longer adds benefit when ibrutinib is used (TRIANGLE).NCCN Category 2A
    First line, older or unfitBendamustine-rituximab + acalabrutinib (ECHO, approved 2025) or BR alone with rituximab maintenance; R-CHOP alternative.NCCN Category 1 (BR + acalabrutinib)
    Relapsed, BTKi-naiveCovalent BTK inhibitor (acalabrutinib, zanubrutinib; ibrutinib ex-US) ± venetoclax (SYMPATICO).NCCN Category 2A
    Relapsed after BTKiBrexucabtagene or lisocabtagene CAR-T; pirtobrutinib; sonrotoclax (2026); allogeneic HSCT in selected patients; bispecific trials.NCCN Category 2A
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  4. State of the art

    Where the field stands

    • Transplant is leaving first-line MCL: TRIANGLE made ibrutinib-containing induction and maintenance the new fit-patient standard.
    • BTK inhibitors sit in first line for older patients (ECHO) and at relapse; pirtobrutinib rescues covalent-BTKi failures.
    • CAR-T (ZUMA-2) gives long remissions after BTKi failure, including in TP53-mutant disease.
    • BCL2 inhibition is back: sonrotoclax approved for relapsed MCL in 2026 with venetoclax combinations close behind.
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  5. History

    How we got here

    1. 1992Cyclin D1 and t(11;14) define MCL
    2. 2008MIPI prognostic index
    3. 2013Ibrutinib: first BTK inhibitor approved
    4. 2017Acalabrutinib approved (ACE-LY-004)
    5. 2019Zanubrutinib approved
    6. 2020Brexucabtagene autoleucel (ZUMA-2)
    7. 2023Pirtobrutinib approved; ibrutinib US MCL indication withdrawn
    8. 2024TRIANGLE and ECHO
    9. 2026Sonrotoclax approved for relapsed MCL
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  6. Pipeline

    What is coming

    • Sonrotoclax (product)
    • Glofitamab (product)
    • Pirtobrutinib (product)
    • Venetoclax (product)
    • BGB-16673 (product)
    • Nemtabrutinib (product)
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  7. Open problems

    What nobody has solved

    • TP53-mutant and blastoid MCL fail chemo-immunotherapy; need CAR-T or bispecific-based first-line trials.
    • MRD-guided treatment duration.
    • Whether CAR-T should precede pirtobrutinib or follow it.
    • Cost and access of indefinite BTK-inhibitor therapy.
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  8. Quiz

    Check understanding

    1. 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

    • TRIANGLE (Lancet 2024): https://doi.org/10.1016/S0140-6736(24)00184-3
    • 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
    • Wikipedia: https://en.wikipedia.org/wiki/Mantle_cell_lymphoma
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480
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