How we treat primary central nervous system lymphoma

• Published in: ESMO open Vol. 6; no. 4; p. 100213
• Main Authors: Calimeri, T., Steffanoni, S., Gagliardi, F., Chiara, A., Ferreri, A.J.M.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-08-2021; Elsevier
• Subjects: high-dose methotrexate; ibrutinib; lenalidomide; primary CNS lymphoma; primary vitreoretinal lymphoma; ibrutinib; primary vitreoretinal lymphoma; high-dose methotrexate; lenalidomide; primary CNS lymphoma
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2021.100213

Primary diffuse large B-cell (DLBCL) lymphoma of the central nervous system (CNS) (PCNSL) is a new lymphoma entity, recognized by the 2017 WHO classification of hematopoietic and lymphoid tumors. Unlike systemic DLBCL, the use of anthracycline-based chemotherapy combinations is associated with disappointing outcomes, due to low CNS bioavailability of related drugs. Therefore, international researchers investigated alternative strategies, mostly including drugs able to cross the blood–brain-barrier at low or high doses, with a progressive improvement in survival. Some effective chemotherapy combinations of high-dose methotrexate (HD-MTX) with alkylating agents and rituximab with or without cytarabine have been tested in international randomized trials and represent the induction treatment in everyday practice, with some variations among different geographical areas. In patients aged 70 years or younger, MATRix (HD-MTX/cytarabine/thiotepa/rituximab) chemotherapy followed by consolidative high-dose chemotherapy plus autologous stem cell transplantation or whole-brain irradiation has been associated with a significant improvement in overall survival. Other treatment options, such as non-myeloablative high-dose chemotherapy, oral drug maintenance, and some targeted drugs like ibrutinib or lenalidomide, are being tested in high-level international trials. These steps toward further effective treatments are motivated by an incessant search for less neurotoxic options. Thanks to international cooperation, we can affirm that PCNSL is a potentially curable tumor, especially in young patients. However, several questions remain unanswered: the optimal treatment for elderly patients as well as the management of intraocular and meningeal disease require further scientific efforts. Beside treatments, advances on molecular and radiological diagnostic tools will increase our knowledge of this disease, allowing the possibility to anticipate diagnosis and to better categorize patients' responses. This article analyzes the available literature in this setting and provides evidence-based recommendations for the management of PCNSL patients.
•HD-MTX based induction and consolidation with HDC/ASCT is our standard of care in young and fit patients (<70 y).•HD-MTX based combinations are the first line treatment in PCNSL candidate to chemotherapy irrespective of age.•Oral maintenance represents an alternative in responding patients not eligible for HDC/ASCT because of age/comorbidities.•Targeted drugs such as BTKi and IMiDs are promising especially in the elderly.•MYD88 and IL10 are optimal biomarkers and might improve suspicion and anticipate PCNSL diagnosis.•A multidisciplinary approach should be applied to reach the best outcomes.