From the Guidelines
The most effective treatment for CNS lymphoma is high-dose methotrexate-based chemotherapy regimens, often including rituximab, as evidenced by the recent study published in 2024 1. This approach has shown significant efficacy and tolerability in patients with primary central nervous system lymphoma (PCNSL), with a 2-year overall survival (OS) rate of 64% and a 6% treatment-related mortality (TRM) rate. The treatment algorithm for newly diagnosed PCNSL involves a combination of chemotherapy, radiotherapy, and autologous stem cell transplantation (ASCT), with the choice of treatment depending on the patient's age, performance status, and response to initial therapy. Some of the commonly used regimens include:
- MATRix (high-dose methotrexate, high-dose cytarabine, rituximab, and thiotepa)
- MBVP (methotrexate, carmustine, etoposide, and methylprednisolone)
- ReMBVP (rituximab, methotrexate, carmustine, etoposide, and methylprednisolone)
- HD-MTX (high-dose methotrexate) with or without rituximab The role of rituximab in the treatment of CNS lymphoma is still a matter of debate, with some studies showing a benefit in terms of event-free survival (EFS) and progression-free survival (PFS) 1. Whole-brain radiation therapy (WBRT) may be used in patients who cannot tolerate chemotherapy or for refractory disease, but it carries significant neurotoxicity risks, especially in older patients. Early diagnosis and treatment are crucial in improving outcomes for patients with CNS lymphoma, as the disease can progress rapidly and cause significant neurological deficits. The prognosis depends on age, performance status, and response to initial therapy, with younger patients generally having better outcomes 1.
From the Research
Overview of CNS Lymphoma
- Primary central nervous system (CNS) lymphoma is a rare and aggressive extranodal non-Hodgkin lymphoma confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement 2.
- It is sensitive to radiation therapy, but whole-brain radiation therapy alone is not sufficient to control the disease and can cause delayed neurotoxicity 2.
Treatment Options
- High-dose methotrexate-based induction chemotherapy is considered standard for newly diagnosed primary CNS lymphoma 3, 2.
- The addition of an alkylating agent and rituximab has shown promising results, with a recent randomized trial demonstrating improved overall survival with the combination of methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) 3.
- Whole-brain irradiation and high-dose chemotherapy supported by autologous stem cell transplantation are effective consolidation strategies in patients with responsive disease 3, 4.
- Immunochemotherapy with rituximab and temozolomide has also shown efficacy in patients with primary or metastatic CNS lymphoma 5.
Treatment of Recurrent Primary CNS Lymphoma
- There is no consensus treatment for refractory or relapsed primary CNS lymphoma, and available strategies are largely based on retrospective analyses 6.
- Patient age, performance status, previously administered treatment, duration of response, and molecular characteristics guide selection of salvage therapy 6.
- High-dose methotrexate-based regimens, such as R-MPV, are often used for remission re-induction, followed by myeloablative chemotherapy and autologous stem cell transplant in curative intent 6.
- Emerging therapies, including bruton tyrosine kinase inhibition, immunomodulatory drugs, immune checkpoint inhibitors, and chimeric antigen receptor T cell therapy, are being investigated for upfront or salvage therapy 6.