Primary central nervous system lymphoma: Consensus, controversies, and future directions

Abstract

Primary central nervous system lymphoma (PCNSL) is an uncommon non-Hodgkin lymphoma for which multiple modalities of treatment are often used, including radiation therapy, chemotherapy with or without autologous stem cell transplant (ASCT), and immunotherapy. The optimal approach to the treatment of PCNSL varies based on patient fitness, age, and comorbid conditions. The cornerstone of therapy remains high-dose methotrexate with or without other chemotherapeutic agents that have activity against PCNSL. Consolidation therapy in the form of whole brain radiation and/or ASCT is offered to select patients. Almost half of the patients experience disease relapse, and the approach to patients with relapsed/refractory disease varies depending on the timing of relapse and the initial treatment. In recent years, several novel agents targeting the B-cell receptor (BCR) pathway have shown activity in early phase trials prompting their ongoing evaluation in larger prospective trials in combinations, as well as their use in the relapsed/refractory setting. Immunotherapy beyond rituximab is an emerging treatment modality that may become part of the therapeutic arsenal. There are various controversial aspects to the optimal treatment of PCNSL, including the use of rituximab, intrathecal chemotherapy, and consolidation therapy. These controversies and the evidence behind the various treatment modalities used in PCNSL are explored in this review.