# Primary CNS lymphoma

Source: https://onco.cc/cancers/primary-cns-lymphoma/  
OnCo record `primary-cns-lymphoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

The open problems are neurotoxicity, the elderly majority who cannot receive intensive therapy, and the lack of a randomised standard beyond induction.

## Fields

- Kind: Cancer
- Last checked: 2026-09-08
- Also known as: PCNSL
- Tags: gap-fill; haematologic; cns
- Group: central nervous system
- Burden: Primary CNS lymphoma affects about 0.5 per 100,000 per year and is ~4% of primary brain tumours, rising in the elderly and in the immunosuppressed.
- Subtypes: Immunocompetent PCNSL (DLBCL, ABC type); AIDS-related / post-transplant PCNSL (EBV-driven); Primary vitreoretinal lymphoma; Primary leptomeningeal lymphoma
- Biomarkers: MYD88 L265P and CD79B mutations (tissue and CSF ctDNA); CSF cytology and flow cytometry; IL-10 in CSF/vitreous; MSKCC and IELSG prognostic scores (age, performance status); Slit-lamp examination for ocular involvement

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/primary-cns-lymphoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/primary-cns-lymphoma/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/primary-cns-lymphoma/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/primary-cns-lymphoma/#finding-it [5 biomarkers, 1 prevalence rows]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/primary-cns-lymphoma/#treating-it [3 settings, 3 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/primary-cns-lymphoma/#evidence [4 trials, 4 key papers, 7 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/primary-cns-lymphoma/#science [8 targets]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/primary-cns-lymphoma/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/primary-cns-lymphoma/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/primary-cns-lymphoma/coming/ [9 medicines, 4 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/primary-cns-lymphoma/data/ [61 connected records]

## Standard of care

- Newly diagnosed, fit (<65-70): Rituximab + high-dose methotrexate + cytarabine ± thiotepa (MATRix) ×4, then high-dose thiotepa-based chemotherapy with autologous transplant (IELSG32, IELSG43). ([Methotrexate](https://onco.cc/drugs/methotrexate/), [Rituximab](https://onco.cc/drugs/rituximab/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [IELSG32](https://onco.cc/trials/ielsg32/), [MATRix/IELSG43](https://onco.cc/trials/ielsg43/))
- Newly diagnosed, older/unfit: High-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. ([Methotrexate](https://onco.cc/drugs/methotrexate/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Rituximab](https://onco.cc/drugs/rituximab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/))
- Relapsed/refractory: Re-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. ([Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Axicabtagene ciloleucel](https://onco.cc/drugs/axicabtagene-ciloleucel/), [Nivolumab](https://onco.cc/drugs/nivolumab/))

## State of the art

- 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Primary_central_nervous_system_lymphoma
- 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

## Connected records

- cancers: [Brain and spinal cord tumours (all types)](https://onco.cc/cancers/brain-tumours/), [Burkitt lymphoma](https://onco.cc/cancers/burkitt-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Intravascular large B-cell lymphoma](https://onco.cc/cancers/intravascular-large-b-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/), [Primary mediastinal (thymic) large B-cell lymphoma](https://onco.cc/cancers/primary-mediastinal-b-cell-lymphoma/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [CAR-T cell therapy](https://onco.cc/technologies/car-t/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRI](https://onco.cc/technologies/mri/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/), [CD19](https://onco.cc/targets/cd19/), [CD20](https://onco.cc/targets/cd20/), [CD79b](https://onco.cc/targets/cd79b/), [Dihydrofolate reductase (DHFR)](https://onco.cc/targets/dhfr/), [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Axicabtagene ciloleucel](https://onco.cc/drugs/axicabtagene-ciloleucel/), [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Nivolumab](https://onco.cc/drugs/nivolumab/), [Rituximab](https://onco.cc/drugs/rituximab/), [Temozolomide](https://onco.cc/drugs/temozolomide/), [Thiotepa](https://onco.cc/drugs/thiotepa/), [Zamtocabtagene autoleucel](https://onco.cc/drugs/zamtocabtagene-autoleucel/)
- companies: [AbbVie (incl. ImmunoGen, Capstan)](https://onco.cc/companies/abbvie/), [Curis](https://onco.cc/companies/curis/), [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/), [Miltenyi Biomedicine](https://onco.cc/companies/miltenyi-biomedicine/), [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- terms: [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/), [Cell of origin (GCB vs ABC)](https://onco.cc/terms/cell-of-origin/), [MYD88 L265P and CXCR4 mutations](https://onco.cc/terms/myd88-l265p/)
- key papers: [IELSG32 first randomisation: the MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) in primary CNS lymphoma](https://onco.cc/key-papers/paper-ielsg32-matrix-induction-ferreri-lancet-haematol-2016/), [IELSG32 second randomisation: whole-brain radiotherapy or autologous stem cell transplant as consolidation in primary CNS lymphoma](https://onco.cc/key-papers/paper-ielsg32-wbrt-vs-asct-consolidation-ferreri-lancet-haematol-2017/), [Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial](https://onco.cc/key-papers/paper-ferreri-leukemia/), [MATRix/IELSG43: high-dose chemotherapy and autologous stem cell transplant versus non-myeloablative consolidation in primary CNS lymphoma](https://onco.cc/key-papers/paper-matrix-ielsg43-asct-consolidation-pcnsl-illerhaus-lancet-2026/)
- trials: [A Study of the Efficacy and Safety of Lisocabtagene Maraleucel (Liso-cel) as First-Line Therapy in Adults With Transplant-Ineligible Primary Central Nervous System Lymphoma](https://onco.cc/trials/nct07015242/), [CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL)](https://onco.cc/trials/nct03328078/), [IELSG32](https://onco.cc/trials/ielsg32/), [MATRix/IELSG43](https://onco.cc/trials/ielsg43/)
- people: [Andrés J. M. Ferreri](https://onco.cc/people/andres-ferreri/), [Benjamin Kasenda](https://onco.cc/people/benjamin-kasenda/)
- collections: [Lymphoma Research Foundation (LRF)](https://onco.cc/collections/lymphoma-research-foundation/), [National Brain Tumor Society (NBTS)](https://onco.cc/collections/national-brain-tumor-society/)
- journals: [Brain tumor pathology](https://onco.cc/journals/brain-tumor-pathology/), [CNS oncology](https://onco.cc/journals/cns-oncology/), [Journal of neuro-oncology](https://onco.cc/journals/journal-of-neuro-oncology/)

---
JSON: https://onco.cc/api/v1/entities/primary-cns-lymphoma.json