Innovative Therapeutic Strategies for Primary CNS Lymphoma

Abstract

Primary central nervous system (CNS) lymphoma (PCNSL) represents 4% of all CNS malignancies and 4–6% of all extranodal lymphomas. Its low incidence is the main reason why it has been difficult to develop guidelines on the treatment and management of PCNSL patients. The lack of consensus around standard therapy and best diagnostic approach, inevitably, affected the outcome of these patients for many years. Current efforts are focusing on: (1) defining the optimal induction and consolidation therapies in fit and frail patients, (2) establishing when and how to use the new non-cytotoxic agents, (3) investigating innovative radiotherapy to mitigate treatment-related neurotoxicity, (4) limiting delays in diagnosis, and (5) improving response assessment with new biological markers and radiological tools. Finally, the complexity of the management of PCNSL patients compels clinicians to provide timely and efficient social, neuropsychological, and physiotherapy support, which is feasible only when there is effective collaboration between the multiple specialists involved in the care of these patients. In the last decade, thanks to multicenter collaborations, important gains have been made, particularly in the front line therapy and in the biological understanding of this disease. The progressive knowledge on molecular profile of PCNSL has justified the recent use of targeted therapy also in these settings of patients. In this review, we discuss important advances in the management of PCNSL and we highlight unresolved questions that should be addressed in the future.