Primary Central Nervous System Lymphoma Management

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma confined to the brain, leptomeninges, eyes or spinal cord. Optimal management integrates precise diagnosis, risk-adapted therapy and careful monitoring to balance disease control with minimising neurotoxicity. High-dose methotrexate–based regimens remain the cornerstone of induction therapy, often combined with the anti-CD20 antibody rituximab and supplemental agents to improve penetration across the blood–brain barrier. Consolidation strategies include autologous haematopoietic stem-cell transplantation or reduced-dose whole-brain radiotherapy to prolong remission while mitigating long-term cognitive effects. Emerging interventions exploit molecular vulnerabilities, such as Bruton's tyrosine kinase inhibition and immune-checkpoint blockade, aiming to enhance response rates in refractory or relapsed settings. Advanced imaging and cerebrospinal fluid biomarkers facilitate early detection of residual disease and guide timely modification of therapy. A multidisciplinary approach—encompassing neurology, oncology, radiology and supportive care—is essential to optimise outcomes and quality of life in this challenging disease.

Research from Nature Portfolio

Seminal work has identified cerebrospinal fluid interleukin-10 and the ratio of interleukin-10 to interleukin-6 as robust diagnostic and prognostic biomarkers for large B-cell PCNSL. Elevated interleukin-10 concentrations in cerebrospinal fluid distinguish PCNSL from other central nervous system disorders with high sensitivity and specificity, and dynamic changes in this cytokine after treatment correlate closely with progression-free survival, offering a non-invasive tool for patient stratification and monitoring of therapeutic efficacy.

Primary Central Nervous System Lymphoma Management publication trend

The graph below shows the total number of articles in primary central nervous system lymphoma management across all publications each year (not limited to Nature Index journals).

Technical terms

Primary Central Nervous System Lymphoma (PCNSL): A lymphoma localised to the brain, spinal cord, eyes or leptomeninges without systemic involvement.

High-dose methotrexate: An intravenous folate antagonist administered at doses sufficient to cross the blood–brain barrier and target malignant lymphocytes.

Rituximab: A monoclonal antibody directed against the CD20 antigen on B lymphocytes, used to enhance tumour cell clearance.

Blood–brain barrier: A selective vascular interface that restricts entry of most drugs into the central nervous system.

Bruton's tyrosine kinase inhibitor (BTK inhibitor): A targeted agent that blocks B-cell receptor signalling critical for lymphoma cell survival.

Tumour microenvironment: The surrounding non-malignant cells, extracellular matrix and signalling molecules that influence tumour behaviour and therapy response.

Biomarker: A measurable biological indicator used for diagnosis, prognosis or monitoring of disease and treatment effect.

References

1. Cerebrospinal Fluid IL-10 and IL-10/IL-6 as Accurate Diagnostic Biomarkers for Primary Central Nervous System Large B-cell Lymphoma. Scientific Reports (2016).
2. Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study. Signal Transduction and Targeted Therapy (2024).
3. Spatial single cell analysis of tumor microenvironment remodeling pattern in primary central nervous system lymphoma. Leukemia (2023).
4. A novel Bruton's tyrosine kinase inhibitor JDB175 shows potent efficacy to suppress central nervous system lymphoma. MedComm (2023).