Understanding Primary CNS Lymphoma (PCNSL)

What is PCNSL?

Primary central nervous system lymphoma is a highly aggressive NHL confined to the CNS, including the brain, spine, cerebrospinal fluid (CSF), and eyes¹. Unlike other lymphomas that spread from other parts of the body, PCNSL starts in the CNS and generally remains confined there. It accounts for about 4% of all newly diagnosed malignant brain tumors and 4% to 6% of all extranodal lymphomas¹.

What Causes PCNSL?

The exact cause of PCNSL is not fully understood. However, it is associated with abnormal growth of B lymphocytes (a type of white blood cell) in the brain. While most PCNSLs are diffuse large B-cell lymphomas (DLBCLs), other types can occur, such as T-cell lymphomas, although these are much rarer¹.

Risk Factors

Individuals with weakened immune systems, such as those with HIV/AIDS or who have undergone organ transplants, have a higher risk of developing PCNSL¹. Other risk factors include:

• Older age (median age at diagnosis is 65 years)
• Epstein-Barr virus (EBV) infection, particularly in immunocompromised individuals
• Possible environmental factors like exposure to pesticides, solvents, or fertilizers²

Symptoms of PCNSL

Since PCNSL affects the brain and nervous system, symptoms can vary depending on the tumor’s location. Common symptoms include:

• Persistent headaches
• Nausea or vomiting
• Cognitive difficulties, including memory loss and confusion
• Weakness or numbness in parts of the body
• Vision problems (blurry vision, double vision, or vision loss)
• Difficulty speaking or understanding speech
• Changes in personality or mood
• Seizures³

It is important to note that these symptoms often develop over weeks, not days, which can lead to a delayed diagnosis.

How is PCNSL Diagnosed?

Several tests are used to diagnose PCNSL, including:

• Magnetic Resonance Imaging (MRI): The primary imaging tool to detect tumors in the brain⁴.
• Lumbar Puncture (Spinal Tap): A procedure that analyzes cerebrospinal fluid for cancerous lymphoma cells⁵.
• Brain Biopsy: A small sample of brain tissue is taken to confirm the presence of lymphoma and differentiate it from other brain tumors¹.

Treatment Options

Treatment for PCNSL typically includes a combination of therapies:

• Magnetic Resonance Imaging (MRI): The primary imaging tool to detect tumors in the brain; however, a CT scan may be used for patients who cannot undergo an MRI¹.
• Lumbar Puncture (Spinal Tap): A procedure that analyzes cerebrospinal fluid for cancerous lymphoma cells¹.
• Brain Biopsy: A small sample of brain tissue is taken to confirm the presence of lymphoma and differentiate it from other brain tumors¹.
• Ocular Assessment: 15% to 25% of patients can have ocular disease at presentation; thus, an ocular assessment should be included in the diagnostic workup¹.

Treatment Options

Treatment for PCNSL typically includes a combination of therapies:

• High-dose Methotrexate-based Chemotherapy: The standard first-line treatment, often combined with other drugs like rituximab, which has shown improved outcomes¹.
• Steroids: Used to reduce brain swelling and can temporarily shrink tumors¹.
• Radiation Therapy: Whole-brain radiation may be used, though its role has diminished due to concerns about neurotoxicity (especially in older patients) and the availability of different medicinal agents¹.
• Autologous Stem Cell Transplantation: Often used as part of a consolidation therapy to kill any cancer cells that may be left in the body after initial therapy, especially in younger patients¹.
• Targeted Therapies and Clinical Trials: Researchers are studying new treatments, including BTK inhibitors, PI3K inhibitors, IRAK4 inhibitors, and immunotherapies, which may improve outcomes. The TakeAim Lymphoma study (NCT03328078) is evaluating emavusertib, an IRAK4 inhibitor, alone and in combination with ibrutinib (a BTK inhibitor), in PCNSL patients with resistance to prior BTK inhibitor treatment and in patients who have completed one line of methotrexate-based therapy and are naïve to BTK inhibitors, showing promising efficacy and an acceptable safety profile in heavily pretreated patients⁴.

What is the Outlook for PCNSL?

The prognosis for PCNSL has improved significantly with advances in treatment. With current treatments, median overall survival is now 30 to 60 months in patients treated with curative intent. However, the disease still has a poor prognosis compared to many other cancers, with a 5-year survival rate of about 30%⁵.

Support and Next Steps

If you or a loved one has been diagnosed with PCNSL, it is important to:

• Work closely with your healthcare team to explore the best treatment options.
• Seek support from patient advocacy groups and online communities.
• Consider enrolling in clinical trials for access to emerging treatments.
• Attend regular follow-up appointments, including MRI scans and neurological assessments, to monitor for recurrence and treatment-related complications.

For more information on PCNSL and ongoing research, visit organizations such as the Leukemia & Lymphoma Society or the American Brain Tumor Association.

References

1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Primary Central Nervous System Lymphoma. 2023.
2. Sousa MG, et al. Primary Central Nervous System Lymphoma: A Literature Review and Update. World Neurosurg. 2017;102:233-240.
3. Ferreri AJ. How I Treat Primary CNS Lymphoma. Blood. 2011;118(3):510-522.
4. Nowakowski G, et al. TakeAim Lymphoma: An Open-Label, Dose-Escalation and Expansion Trial of Emavusertib Monotherapy and Emavusertib Plus Ibrutinib in Relapsed/Refractory B-Cell Non-Hodgkin Lymphomas. Blood. 2023;142(Supplement 1):4497.
5. Rarediseaseadvisor.com. Primary Central Nervous System Lymphoma Life Expectancy. 2024.