Recent advances in primary CNS lymphoma

This review highlights the recent advances in the pathogenesis and treatment of primary CNS lymphoma (PCNSL) in the immunocompetent population.

High-dose methotrexate (MTX)-based chemotherapy followed by whole brain radiotherapy represents the standard treatment. However, combined treatment exposes the patients to the risk of delayed neurotoxicity. Although this complication is less frequent and severe in young patients (less than 60 years) than in the elderly, neuropsychometric evaluation suggests that it is underestimated in this population. Recent trials, adding further to previous studies, suggest that high-dose MTX-based chemotherapy with deferred radiotherapy allows comparable results to those reported after combined chemoradiotherapy, with much better neurocognitive preservation. Intensive chemotherapy with autologous stem cell transplantation has shown a promising activity in relapsed or refractory PCNSL, but its value as first-line treatment compared with conventional treatment remains questionable. New therapeutic agents such as temozolomide, topotecan, or intrathecal rituximab (anti-CD20 monoclonal antibody) have demonstrated a modest but true activity as single-agent therapy in relapsed PCNSL and are of interest, in terms of their good safety profile, for inclusion in new polychemotherapy regimen as primary treatment.

In the elderly, MTX-based chemotherapy seems to be the best approach to achieve effective tumor control without compromising patient quality of life. Future trials should first analyze the value of radiotherapy as consolidation treatment in young patients (less than 60 years) who have achieved a remission after induction chemotherapy in a randomized study. Other trials are needed to further evaluate intensive chemotherapy with autologous stem cell transplantation both as primary and salvage therapy; and to investigate new drug combinations with high-dose MTX.