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

Treatment for Primary Central Nervous System (CNS) Lymphoma

The standard treatment for primary CNS lymphoma involves high-dose methotrexate-based chemotherapy regimens, with the MATRix regimen (high-dose methotrexate, high-dose cytarabine, rituximab, and thiotepa) followed by consolidation therapy (either autologous stem cell transplantation or whole-brain radiotherapy) being the most effective approach for eligible patients. 1

First-Line Treatment Approach

Patient Stratification

• Treatment selection should consider not only age but also performance status, organ function, comorbidities, and frailty 1
• Patients should be managed by a multidisciplinary team at specialized centers with experience in PCNSL 1

Induction Therapy

• High-dose methotrexate (HD-MTX) is the cornerstone of treatment, with doses of at least 3 g/m² administered over 2-4 hours 1
• Combination regimens are superior to HD-MTX monotherapy:
  • The addition of high-dose cytarabine to HD-MTX significantly increases response rates (69% vs 40%) and progression-free survival 2
  • The MATRix regimen (HD-MTX, HD-cytarabine, rituximab, and thiotepa) has shown the best outcomes with 7-year overall survival of 56% 1

For Fit Patients (≤65 years with ECOG PS 0-3 or ≤70 years with ECOG PS ≤2):

• MATRix regimen is recommended as the standard induction therapy 1
• Alternative regimens include:
  • HD-MTX + HD-cytarabine combinations 1
  • MBVP (methotrexate, carmustine, etoposide, methylprednisolone) 1
  • Methotrexate-temozolomide-based regimens 3, 4

For Elderly or Less Fit Patients:

• Less intensive HD-MTX-based regimens are recommended 1
• Options include HD-MTX monotherapy or combinations with temozolomide or procarbazine 1

Consolidation Therapy

• After successful induction, consolidation therapy is essential to improve long-term outcomes 1
• Two main consolidation strategies:
  • High-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT) 1
  • Whole-brain radiotherapy (WBRT) 1
• Both approaches have shown similar efficacy, with 7-year overall survival reaching 70% after MATRix induction followed by either consolidation method 1

Treatment for Relapsed/Refractory Disease

• Patients with relapsed/refractory PCNSL should be enrolled in clinical trials when possible 1
• Treatment approach depends on timing of relapse and patient fitness:
  • For fit patients with early relapse: HD-ifosfamide or HD-cytarabine-based regimens followed by ASCT or WBRT 1
  • For unfit patients: WBRT or single-agent therapy with ibrutinib, lenalidomide, or temozolomide 1
  • For late relapse: Re-treatment with HD-MTX-based regimen followed by consolidation 1

Special Considerations

• Neurotoxicity risk increases with combined chemoradiotherapy, particularly in patients >60 years 1
• Response assessment should follow International PCNSL Collaborative Group criteria with MRI every two cycles during induction and 2 months after consolidation 1
• Novel approaches under investigation include:
  • BTK inhibitors (ibrutinib, tirabrutinib) 1
  • Immunomodulators (lenalidomide, pomalidomide) 1
  • Immune checkpoint inhibitors (pembrolizumab, nivolumab) 1
  • CAR-T cell therapy 1

Treatment Algorithm

1. Confirm diagnosis with stereotactic biopsy
2. Assess patient fitness (age, performance status, organ function)
3. For fit patients: MATRix induction (4 cycles) followed by consolidation with either HDC-ASCT or WBRT
4. For elderly/unfit patients: Less intensive HD-MTX-based regimens
5. Monitor response with MRI after every 2 cycles
6. For relapsed disease: Consider salvage therapy based on prior treatment and time to relapse

This approach has demonstrated the best outcomes in terms of survival and quality of life for patients with PCNSL 1.