Management of primary central nervous system lymphoma (PCNSL) includes induction 
and consolidation therapies in newly diagnosed patients, as well as second-line 
therapy in relapsed or refractory patients. The current standard-of-care 
induction therapy involves methotrexate (MTX)-based multi-agent 
immunochemotherapy with rituximab, methotrexate, procarbazine, and vincristine. 
Deferral or dose reduction of radiation therapy is considered in consolidation 
therapy, especially in elderly patients who carry a high risk of 
radiation-induced delayed neurotoxicity. Since elderly patients comprise the 
main population of PCNSL, minimally toxic treatments that are effective and 
feasible for them are strongly needed. For second-line therapy, rechallenge 
using MTX-based chemotherapy (in patients with a prior durable response to 
MTX-based chemotherapy) or radiation therapy is considered. Bruton's tyrosine 
kinase inhibitor tirabrutinib (for relapsed and refractory PCNSL) and high-dose 
chemotherapy with autologous stem cell transplantation support using thiotepa 
and busulfan (BuTT) were approved by the Japanese Ministry of Health and Welfare 
in March 2020 and has recently become available for clinical practice. While 
these novel treatments seem promising, the optimal use of these treatments along 
with the standard-of-care therapy of PCNSL should be defined and investigated in 
clinical trials.