Primary central nervous system lymphoma: advances in treatment strategies

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare subtype of aggressive non-Hodgkin lymphoma originating within the CNS. Whole brain irradiation (WBRT) has been utilized in combination with high-dose methotrexate (HD-MTX), unfortunately with a high rate of late neurocognitive decline, particularly in the elderly. HD-MTX-based combination chemotherapy regimens have been developed as induction therapy for PCNSL and shown to improve response rates. Consolidation treatment, such as reduced-dose WBRT or high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is vital to controlling the disease. Two phase II trials randomizing PCNSL patients to WBRT or HDT-ASCT were recently published, showing comparable survival but better neurocognitive function in patients receiving HDT-ASCT. A key agent in HDT-ASCT for PCNSL is thiotepa, which, however, has been unavailable in Japan since 2011. Therefore, a clinical trial of HDT-ASCT with thiotepa was performed, and we are currently awaiting drug approval. Several targeted drugs are being trialed in patients with relapsed or refractory PCNSL. The treatment strategy of PCNSL is still developing to improve survival and reduce toxicity.