2022 Volume 31 Issue 1 Pages 20-30
Primary central nervous system lymphoma (PCNSL) develops more often in the elderly population. Its incidence has been increasing in recent years and it is accounting for 4.9% of brain tumors. Most PCNSLs are histologically classified as diffuse large B-cell lymphomas. Among these, CD10 positivity is lower and MUM1 positivity is higher in PCNSL than in non-PCNSL, which results in higher dominance of the non-germinal-center B-cell-like type in PCNSLs. The frequency of mutations in MYD88 and CD79B genes is higher in PCNSL than in non-PCNSL, which leads to the activation of the B-cell-receptor signaling pathway. Bruton's tyrosine kinase (BTK) is a key molecule in the B-cell-receptor signaling pathway. Therefore, it is a potential molecular target for the treatment of PCNSL. Tirabrutinib, a second-generation BTK inhibitor, has been developed and approved in Japan for the treatment of recurrent or refractory PCNSL. Current challenges include increasing the intensity of chemotherapy while reducing the dose or avoidance of whole-brain radiotherapy (WBRT), as brain damage and late effects, including leukoencephalopathy, are not negligible not only in elderly patients but also in young patients. In Japan, the combination of rituximab, high-dose methotrexate, procarbazine, and vincristine, the so-called R-MPV therapy, is being recognized as a new standard induction chemotherapy. R-MPV therapy followed by reduced-dose WBRT and high-dose cytarabine is well tolerated and shows better outcomes than the previous standard high-dose methotrexate therapy followed by WBRT. High-dose chemotherapy with autologous peripheral blood stem cell transplantation in young patients and appropriate treatment selection at the time of recurrence are essential for further improvement of treatment outcomes.
