Treatment Options for Primary CNS Lymphoma
High-dose methotrexate-based chemotherapy regimens are the cornerstone of treatment for primary central nervous system lymphoma (PCNSL), with the MATRix regimen (high-dose methotrexate, high-dose cytarabine, thiotepa, and rituximab) showing the best outcomes for eligible patients. 1, 2
Patient Stratification
- Treatment selection should consider age, performance status, organ function, comorbidities, and frailty rather than age alone 1
- Patients should be managed by a multidisciplinary team at specialized centers with experience in PCNSL 1, 2
- Enrollment in prospective clinical trials should be prioritized whenever possible 1
First-Line Treatment
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, 2
- Combinations of HD-MTX with other agents that cross the blood-brain barrier are recommended over HD-MTX monotherapy 1
- The MATRix regimen has demonstrated superior outcomes with significantly improved 7-year progression-free survival (52%) and overall survival (56%) compared to other regimens 1, 2
- Other effective regimens include ReMBVP, rituximab-HD-MTX-carmustine-etoposide-prednisone, ReMPV, and ReMT 1
- Adding rituximab to HD-MTX-based regimens is common practice, though not FDA or EMA approved specifically for PCNSL 1, 3
Consolidation Therapy
- After successful induction, consolidation therapy is essential to improve long-term outcomes 1, 2
- Two main consolidation strategies exist:
- Both approaches have shown similar efficacy, with 7-year overall survival reaching 70% after MATRix induction followed by either consolidation method 1, 2
- Thiotepa-based ASCT conditioning regimens are recommended, combined with either busulfan or carmustine 1
Special Patient Populations
Elderly or Unfit Patients
- WBRT should be avoided or deferred in elderly patients due to high risk of disabling neurocognitive impairment 1
- Reduced-dose WBRT (23.4 Gy) is an option for responsive disease after induction, though long-term cognitive effects remain unclear 1
- Watchful waiting can be considered in elderly patients achieving complete remission after induction 1
- Maintenance with oral alkylating agents or immunomodulators like lenalidomide can be considered individually 1
- For patients unfit for HD-MTX-based chemotherapy (<15% of cases), options include:
HIV-Associated PCNSL
- Rituximab plus HD-MTX (3 g/m²) combined with fully active antiretroviral therapy is recommended 3
- This approach has demonstrated good outcomes with a median overall survival of 5.7 years and 5-year overall survival rate of 48% 3
- Concurrent antiretroviral therapy is essential for immune reconstitution 3
Treatment for Relapsed/Refractory Disease
- Patients with relapsed/refractory PCNSL should be enrolled in clinical trials when possible 1, 2
- Treatment approach depends on timing of relapse and patient fitness 1, 2:
- Novel approaches showing promise include:
Response Assessment and Monitoring
- Response should follow International PCNSL Collaborative Group criteria 1, 2
- Gadolinium-enhanced MRI of the brain should be performed every two courses during induction and 2 months after consolidation 1
- Ocular and CSF exams should be added if these were involved at baseline 1
Clinical Pitfalls and Considerations
- Neurotoxicity risk increases with combined chemoradiotherapy, particularly in patients >60 years 2, 4
- Negative CSF cytology does not exclude CNS lymphoma; flow cytometry has higher sensitivity 4
- CHOP-like regimens have proven ineffective due to insufficient blood-brain barrier penetration 1, 6
- The 5-year survival rate of all treated patients is approximately 31% according to registry data, highlighting the need for continued research 6