Treatment for Primary Central Nervous System (CNS) Lymphoma
The standard treatment for primary CNS lymphoma is high-dose methotrexate (HD-MTX)-based chemotherapy regimens, with the MATRix regimen (HD-MTX, high-dose cytarabine, thiotepa, and rituximab) being the most effective approach for eligible patients, followed by consolidation with either high-dose chemotherapy with autologous stem cell transplantation or whole-brain radiotherapy. 1, 2
Patient Stratification and Evaluation
- All patients should be evaluated by a multidisciplinary team at specialized centers with experience in PCNSL, including neurosurgeons, neuroradiologists, haematopathologists, haematologists, oncologists, and radiation oncologists 3
- Treatment selection should consider age, performance status, organ function, comorbidities, and frailty rather than age alone 3
- Before initiating treatment, patients require assessment of:
- Renal function (creatinine clearance >50 ml/min)
- Hepatic function
- Cardiac function (left ventricular ejection fraction >45%) 3
- Response assessment should follow International PCNSL Collaborative Group criteria with MRI every two cycles during induction and 2 months after consolidation 3, 1
First-Line Treatment Algorithm
Induction Therapy
- HD-MTX is the cornerstone of all treatment regimens at a minimum dose of 3 g/m² delivered in a 2-4 hour infusion 3
- For fit patients, combination regimens are superior to HD-MTX monotherapy 3
- The MATRix regimen (HD-MTX, high-dose cytarabine, thiotepa, and rituximab) has shown the best outcomes with 7-year overall survival of 56% 1, 4
- Other effective regimens include:
- The benefit of adding rituximab remains unclear but is commonly included in modern regimens 3, 6
Consolidation Therapy
- After successful induction, consolidation therapy is essential for improving long-term outcomes 3, 1
- Two main consolidation strategies with similar efficacy:
- WBRT should be avoided or deferred in elderly patients due to high risk of neurotoxicity 3, 5
- Reduced-dose WBRT (23.4 Gy) is an option for patients with responsive disease after induction, but long-term cognitive effects remain unclear 3, 6
Treatment for Specific Patient Populations
Elderly or Unfit Patients
- For elderly patients in complete remission after induction, options include:
- For patients unfit for HD-MTX-based chemotherapy (<15% of patients):
HIV-Associated PCNSL
- Recommended treatment is rituximab plus HD-MTX (3 g/m²) combined with fully active antiretroviral therapy 7
- This approach has demonstrated good outcomes with 5-year overall survival rates of 48-67% 7
Treatment for Relapsed/Refractory Disease
- Clinical trial enrollment should be prioritized when available 3, 1
- For MTX-sensitive relapse, re-exposure to HD-MTX-based regimens is an option 3, 2
- HDC-ASCT is recommended for fit patients with chemosensitive disease 3, 2
- Novel approaches under investigation include BTK inhibitors, immunomodulators, and immune checkpoint inhibitors 1, 5
Clinical Pitfalls and Considerations
- Neurotoxicity risk increases significantly with combined chemoradiotherapy, particularly in patients >60 years 3, 1
- CHOP-like regimens are ineffective due to poor blood-brain barrier penetration 3
- Intrathecal chemotherapy is not recommended in routine practice except for patients with CSF dissemination who cannot receive HD-MTX at 3 g/m² 3, 2
- Intravitreal chemotherapy is reserved for patients with persistent intraocular lymphoma after first-line treatment 3