What is the recommended treatment approach for primary central nervous system (CNS) lymphoma in patients with human immunodeficiency virus (HIV)?

Treatment Approach for Primary CNS Lymphoma in HIV

For patients with HIV-associated primary CNS lymphoma (HIV-PCNSL), the recommended first-line treatment is rituximab plus high-dose methotrexate (3 g/m²) combined with fully active antiretroviral therapy (ART). 1

First-Line Treatment Algorithm

Standard Approach:

• Rituximab plus high-dose methotrexate (HD-MTX) at 3 g/m² combined with fully active ART is the recommended first-line treatment for most patients with HIV-PCNSL 1
• This regimen has demonstrated good outcomes with a retrospective study showing median overall survival of 5.7 years and a 5-year overall survival rate of 48% 1
• A prospective trial using rituximab-HD-MTX showed an estimated 5-year overall survival rate of 67% 1

For Patients with Well-Controlled HIV:

• In patients already established on effective ART with well-controlled HIV where the lymphoma pathogenesis resembles that of immunocompetent patients, consider a more intensive approach 1
• The MATRix regimen (rituximab, methotrexate, cytarabine, thiotepa) followed by autologous stem cell transplantation (ASCT) should be considered 1
• The MATRix regimen has shown excellent long-term outcomes in immunocompetent patients with a 7-year overall survival of 56% 2
• Patients treated with MATRix followed by consolidation have achieved a 7-year overall survival of 70% 2

Treatment Considerations

Importance of Antiretroviral Therapy:

• Concurrent ART is essential for immune reconstitution and may contribute to long-term disease control 1
• Effective HIV control improves tolerance to chemotherapy and overall outcomes 1

Response Assessment:

• Brain MRI with contrast is the gold standard to assess treatment response 4-8 weeks after chemotherapy 1
• After initial assessment, symptom-driven investigations without routine rescanning is a reasonable approach 1

Management of Relapsed/Refractory Disease

Treatment Options:

• Both whole-brain radiotherapy (WBRT) and HD-MTX have been used in relapsed/refractory HIV-PCNSL 1
• WBRT is a reasonable option for patients with chemorefractory disease, those who cannot tolerate HD-MTX, or for palliative intent in patients with poor functional status 1
• Thiotepa-based intensive chemotherapy followed by ASCT (if disease is chemosensitive) is another option 1
• Novel agents such as lenalidomide or Bruton tyrosine kinase inhibitors may be considered if available 1

Secondary CNS Lymphoma in HIV

• For HIV-associated secondary CNS lymphoma (HIV-SCNSL), treatment should be similar to that used for HIV-negative patients 1
• The MARIETTA approach (three courses of MATRix followed by three courses of R-ICE and consolidation with carmustine-thiotepa and ASCT) should be considered for chemosensitive disease 1
• CAR-T therapy may also be considered based on encouraging responses in HIV-negative patients 1

Pitfalls and Caveats

• Rituximab is not approved by the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for PCNSL treatment, though clinical evidence supports its use 1
• Careful monitoring for infections is essential during treatment, as immunosuppression from both HIV and chemotherapy increases infection risk 3, 4
• Differential diagnosis between PCNSL and cerebral toxoplasmosis is crucial in HIV patients with brain lesions before initiating treatment 3
• Prognosis historically has been poor with median survival of 2-4 months, but patients treated with chemotherapy do significantly better (median survival 1.5 years) 3