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Primary central nervous system lymphoma

Nature Reviews Disease Primers volume 9, Article number: 29 (2023) Cite this article

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Abstract

Primary central nervous system lymphoma (PCNSL) is a diffuse large B cell lymphoma in which the brain, spinal cord, leptomeninges and/or eyes are exclusive sites of disease. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Other factors such as T cells, macrophages or microglia, endothelial cells, chemokines, and interleukins, probably also have important roles. Clinical presentation varies depending on the involved regions of the CNS. Standard of care includes methotrexate-based polychemotherapy followed by age-tailored thiotepa-based conditioned autologous stem cell transplantation and, in patients unsuitable for such treatment, consolidation with whole-brain radiotherapy or single-drug maintenance. Personalized treatment, primary radiotherapy and only supportive care should be considered in unfit, frail patients. Despite available treatments, 15–25% of patients do not respond to chemotherapy and 25–50% relapse after initial response. Relapse rates are higher in older patients, although the prognosis of patients experiencing relapse is poor independent of age. Further research is needed to identify diagnostic biomarkers, treatments with higher efficacy and less neurotoxicity, strategies to improve the penetration of drugs into the CNS, and roles of other therapies such as immunotherapies and adoptive cell therapies.

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Fig. 1: Biological and molecular properties of neoplastic cells in PCNSL.
Fig. 2: PCNSL histopathology.
Fig. 3: Biological and molecular properties of the microenvironment in PCNSL.
Fig. 4: Intraocular infiltration.
Fig. 5: MRI findings in a patient with primary central nervous system lymphoma.
Fig. 6: Therapeutic flowchart for patients with newly diagnosed PCNSL.

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Author information

Author notes

  1. These authors contributed equally: Maurilio Ponzoni, Tracy T. Batchelor.

Authors and Affiliations

  1. Lymphoma Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Andrés J. M. Ferreri & Teresa Calimeri

  2. Department of Haematology, University College Hospital, London, UK

    Kate Cwynarski

  3. Cancer and Neurotoxicity Clinic and Brain Repair Research Program, Massachusetts General Hospital Cancer Center, Boston, MA, USA

    Jorg Dietrich

  4. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Christian Grommes

  5. APHP, Groupe Hospitalier Salpêtrière, Sorbonne Université, IHU, ICM, Service de Neurologie 2, Paris, France

    Khê Hoang-Xuan

  6. Department of Radiology, Neuroradiology Division, Mayo Clinic, Phoenix, AZ, USA

    Leland S. Hu

  7. Clinic of Hematology, Oncology and Palliative Care, Klinikum Stuttgart, Stuttgart, Germany

    Gerald Illerhaus

  8. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Lakshmi Nayak & Tracy T. Batchelor

  9. Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Maurilio Ponzoni

  10. Ateneo Vita-Salute San Raffaele, Milan, Italy

    Maurilio Ponzoni

Authors
  1. Andrés J. M. Ferreri
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  2. Teresa Calimeri
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  3. Kate Cwynarski
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  4. Jorg Dietrich
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  5. Christian Grommes
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  6. Khê Hoang-Xuan
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  7. Leland S. Hu
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  8. Gerald Illerhaus
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  9. Lakshmi Nayak
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  10. Maurilio Ponzoni
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  11. Tracy T. Batchelor
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Contributions

Introduction (A.J.M.F.); Epidemiology (A.J.M.F. and K.H.-X.); Mechanisms/pathophysiology (A.J.M.F., C.G. and M.P.); Diagnosis, screening and prevention (A.J.M.F., T.C., L.S.H., M.P. and T.T.B.); Management (A.J.M.F., T.C., K.C., K.H.-X., G.I., L.N. and T.T.B.); Quality of life (A.J.M.F. and J.D.); Outlook (A.J.M.F.); Overview of Primer (A.J.M.F.).

Corresponding author

Correspondence to Andrés J. M. Ferreri.

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Competing interests

A.J.M.F. has received speaker fees from Adienne, AstraZeneca, Bristol Myers Squibb, Gilead, Novartis and Roche; was a member of advisory boards of Abbvie, AstraZeneca, Bristol Myers Squibb, Genmab, Gilead, Incyte, Juno, Novartis, PletixaPharm and Roche; currently receives research grants from Abbvie, Amgen, ADC Therapeutics, Bayer HealthCare Pharmaceuticals, Beigene, Bristol Myers Squibb, Genmab, Gilead, Hutchison Medipharma, Incyte, Janssen Research & Development, MEI Pharma, Novartis, Pfizer, Pharmacyclics, PletixaPharm, Protherics, Roche and Takeda; and holds patents on NGR-hTNF-α in brain tumours and NGR-hTNF/R-CHOP in relapsed or refractory PCNSL and SNGR-hTNF in brain tumours. K.C. has received speaker fees from Roche, Takeda, Kite, Gilead, Incyte and Celgene/BMS as well as consulting fees from Roche, Takeda, Celgene, Atara, Gilead, KITE, Janssen and Incyte. J.D. has been a consultant for Blue Earth Diagnostics, Magnolia and Unum Therapeutics; has received research support from Beacon Biosignals, Boehringer Ingelheim, Bristol Myers Squibb, Medimmune, Acerta Pharma and Orbus Therapeutics; and has received royalties from Wolters Kluwer for serving as an author for UpToDate. C.G. has received research support from Pharmacyclics, Bayer, and Bristol Myers Squibb and has acted as a consultant for Kite, BTG and ONO. K.H.-X. has received consulting fees from BTG. L.S.H. is co-founder of Precision Oncology Insights. G.I. has received speaker fees from Roche and Gilead; was a member of advisory boards of Gilead, Incyte, and Roche and received research fundings from the German Ministry of Science. L.N. has consulted for Ono Pharmaceutical, Genmab and BraveBio, has received clinical trial research support from Merck, Kazia and AstraZeneca, and delivered Continuing Medical Education lectures for Oakstone Medical Publishing and Neurology Audio Digest. T.C. has received consulting fees from Janssen-Cilag. M.P. and T.T.B. declare no competing interests.

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Nature Reviews Disease Primers thanks M. Deckert, M. Holdhoff, R. Yamanaka and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Ferreri, A.J.M., Calimeri, T., Cwynarski, K. et al. Primary central nervous system lymphoma. Nat Rev Dis Primers 9, 29 (2023). https://doi.org/10.1038/s41572-023-00439-0

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