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Teaching pack: Primary CNS 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 · central nervous system

    Primary CNS lymphoma

    Primary CNS lymphoma is a lymphoma confined to the brain, eyes and spinal fluid. Unlike most brain tumours it is chemo-sensitive: high-dose methotrexate-based treatment cures a substantial minority, and consolidation with a stem-cell transplant has replaced whole-brain radiation for the fit.

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

    In two paragraphs

    PCNSL is almost always a diffuse large B-cell lymphoma of activated B-cell type, with near-universal MYD88 L265P and CD79B mutations and 9p24 (PD-L1) gains. It presents with focal deficits or cognitive change; diagnosis needs stereotactic biopsy before steroids, plus eye examination and CSF cytology/flow.

    Induction is high-dose methotrexate (≥3 g/m²) combined with cytarabine, thiotepa and rituximab (MATRix, IELSG32) or with temozolomide/procarbazine (R-MPV). Consolidation with high-dose chemotherapy and autologous transplant matches or beats whole-brain radiotherapy with far less neurotoxicity (IELSG32, PRECIS), so radiation is reserved for the unfit or as salvage. Older patients receive methotrexate-based regimens with maintenance (temozolomide, lenalidomide or ibrutinib). Relapsed disease responds to ibrutinib, lenalidomide and PD-1 blockade transiently; CD19 CAR-T crosses into the CNS with responses in small series.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    Newly diagnosed, fit (<65-70)Rituximab + high-dose methotrexate + cytarabine ± thiotepa (MATRix) ×4, then high-dose thiotepa-based chemotherapy with autologous transplant (IELSG32, IELSG43).NCCN Category 2A
    Newly diagnosed, older/unfitHigh-dose methotrexate with temozolomide, procarbazine or rituximab (e.g. MT-R, R-MP), then maintenance (temozolomide, lenalidomide) or reduced-dose WBRT; ibrutinib-based induction in trials.not mapped
    Relapsed/refractoryRe-induction with methotrexate if durable first remission; ibrutinib, lenalidomide-rituximab, high-dose chemotherapy/ASCT if not done, WBRT; CD19 CAR-T and PD-1 inhibitors in trials or off-label.not mapped
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  4. State of the art

    Where the field stands

    • Cure is possible: about half of fit patients treated with MATRix and autologous transplant are alive and disease-free at seven years (IELSG32).
    • Transplant consolidation has largely replaced whole-brain radiotherapy, avoiding its dementing neurotoxicity.
    • CSF ctDNA (MYD88 L265P) enables less invasive diagnosis and response monitoring.
    • BTK inhibition and CD19 CAR-T show CNS penetration and activity, though durability is limited outside transplant.
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  5. History

    How we got here

    1. 1980High-dose methotrexate shown active in PCNSL
    2. 1992Methotrexate before radiotherapy doubles survival (DeAngelis)
    3. 2010G-PCNSL-SG-1: omitting WBRT does not shorten survival
    4. 2016IELSG32: MATRix induction
    5. 2017Autologous transplant equals WBRT with less neurotoxicity
    6. 2017Ibrutinib active in relapsed PCNSL
    7. 2022IELSG32 7-year update confirms cures
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  6. Pipeline

    What is coming

    • Ibrutinib (product)
    • Axicabtagene ciloleucel (product)
    • Lenalidomide (product)
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  7. Open problems

    What nobody has solved

    • Most patients are over 65 and cannot tolerate curative-intent therapy.
    • Neurocognitive decline from disease and therapy.
    • No randomised evidence for maintenance strategies.
    • Vitreoretinal lymphoma relapse and CNS spread.
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  8. Quiz

    Check understanding

    1. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
      Answer
      About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
    2. 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.
    3. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
      Answer
      SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.
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  9. Sources

    Read the primary sources

    • IELSG32 long-term (Leukemia 2022): https://doi.org/10.1038/s41375-022-01582-5
    • NCCN Guidelines: CNS Cancers: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425
    • NCI PDQ: primary CNS lymphoma: https://www.cancer.gov/types/lymphoma/patient/primary-cns-lymphoma-treatment-pdq
    • Wikipedia: https://en.wikipedia.org/wiki/Primary_central_nervous_system_lymphoma
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1425
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