Primary CNS lymphoma treatment: Current status and future directions

Primary central nervous system lymphoma (PCNSL) is a rare variant of non-Hodgkin’s lymphoma that is confined to the central nervous system. It comprises approximately 2 to 7% of primary central nervous system tumors and its incidence has been increasing in the immunocompetent, elderly patient population in Japan. Although high-dose methotrexate-based chemotherapy and whole-brain radiation therapy (WBRT) has improved disease control and survival in patients with PCNSL, most patients eventually experience a relapse, and uncontrolled PCNSL remains the primary cause of death. The aims of this review are to understand current treatment modalities and their problems, and novel trials that aim to improve survival and functional outcome. Currently, multiple treatment regimens using high-dose MTX-based multiagent chemotherapy have been reported, but overall survival has plateaued around 3 to 4 years. Also, WBRT produces considerable neurotoxicity, especially in elderly patients. To improve functional outcome, it has been reported that deferring WBRT was associated with reduced neurotoxicity without worsening the prognosis. To reduce recurrence after MTX-based chemotherapy, encouraging results have been published recently of trials using high-dose myeloablative chemotherapy with autologous hematopoietic stem cell transplantation (HDCT/ASCT). This strategy could replace consolidation radiotherapy. Clarification of pathogenesis and pathophysiology, including molecular analysis, is indispensable in developing new treatment modalities. Additionally, it is imperative that novel treatment modalities should be developed to improve survival and functional outcome. Deferral of radiation therapy by introducing HDCT/ASCT is one such candidate.