What is the typical treatment for primary central nervous system (CNS) lymphoma?

Treatment for Primary CNS Lymphoma

High-dose methotrexate-based chemotherapy regimens, particularly the MATRix regimen (HD-MTX, high-dose cytarabine, thiotepa, and rituximab), are the standard treatment for primary CNS lymphoma, showing the best outcomes with 7-year overall survival of 56%. 1

First-Line Treatment Approach

• Treatment selection must consider patient factors including age, performance status, organ function, comorbidities, and frailty 1
• Patients should be managed by multidisciplinary teams at specialized centers with PCNSL experience 1
• High-dose methotrexate (HD-MTX) is the cornerstone of treatment, with minimum doses of 3 g/m² administered over 2-4 hours 1
• For patients with good performance status, the MATRix regimen has demonstrated superior outcomes compared to other regimens 2
• The addition of high-dose cytarabine to methotrexate significantly improves complete remission rates (46% vs 18%) and overall response rates (69% vs 40%) compared to methotrexate alone 3

Consolidation Therapy

• After successful induction, consolidation therapy is essential for improving long-term outcomes 1
• Two main consolidation strategies have shown similar efficacy:
  • High-dose chemotherapy with autologous stem cell transplantation 1
  • Whole-brain radiotherapy 1
• Both approaches have demonstrated 7-year overall survival rates of approximately 70% when following MATRix induction 1

Treatment Algorithm Based on Patient Characteristics

For Fit Patients (Good Performance Status)

• MATRix regimen (HD-MTX, high-dose cytarabine, thiotepa, and rituximab) as induction therapy 1, 2
• Followed by consolidation with either:
  • High-dose chemotherapy with autologous stem cell transplantation 1
  • Whole-brain radiotherapy 1

For Elderly or Less Fit Patients

• HD-MTX-based regimens with dose adjustments based on renal function and comorbidities 2
• Consider avoiding whole-brain radiotherapy in patients >60 years due to increased neurotoxicity risk 1, 2

For HIV-Associated PCNSL

• Rituximab plus high-dose methotrexate (3 g/m²) combined with fully active antiretroviral therapy 4
• This approach has shown good outcomes with a median overall survival of 5.7 years and a 5-year overall survival rate of 48% 4

Management of Relapsed/Refractory Disease

• Clinical trial enrollment should be prioritized when possible 1
• Treatment approach depends on timing of relapse and patient fitness 1
• Options for fit patients include:
  • High-dose ifosfamide or high-dose cytarabine-based regimens 1
  • Followed by autologous stem cell transplantation or whole-brain radiotherapy 1

Response Assessment and Monitoring

• Follow International PCNSL Collaborative Group criteria 1
• MRI evaluation every two cycles during induction and 2 months after consolidation 1

Important Clinical Considerations and Pitfalls

• Neurotoxicity risk increases significantly with combined chemoradiotherapy, particularly in patients >60 years 1, 2
• Comprehensive diagnostic evaluation should include MRI of brain/spine with contrast and CSF examination with cytology and flow cytometry 2
• Negative CSF cytology does not exclude CNS lymphoma; flow cytometry has higher sensitivity 2
• Grade 3-4 hematological toxicity is common with combination regimens (92% with methotrexate plus cytarabine vs 15% with methotrexate alone) 3
• Alternative regimens incorporating temozolomide have shown promising results with complete response rates of 85% and 5-year overall survival of 77% in some studies 5