SS-5 Current management of primary central nervous system lymphoma

Primary CNS Lymphomas (PCNSLs) is a highly aggressive malignant tumor with poor prognosis and increasing incidence in elderly patients. High-dose methotrexate (HD-MTX) followed by whole-brain radiation therapy (WBRT) improves survival in PCNSLs. Several HD-MTX–based regimens, in combination with alkylating agents and rituximab, have been developed that can achieve high and durable complete response rates in patients with newly diagnosed PCNSL. In Japan, the R-MPV regimen using rituximab, HD-MTX, procarbazine, and vincristine has been recognized as the standard treatment for initial induction for newly diagnosed PCNSL. The optimal consolidative therapy for patients with disease responsive to induction chemotherapy is not yet defined. WBRT at standard dose (30–45 Gy) has a risk of neurotoxicity. To minimize the effects of delayed neurotoxicity, high-dose chemotherapy supported by autologous stem cell transplantation, reduced dose WBRT (23.4Gy), non-myeloablative chemotherapy, and maintenance chemotherapy have been addressed in large randomized trials. Gene expression profiling has provided insights into the pathogenesis of PCNSL. Recent insight into the pathophysiology of PCNSL has led to the investigation of targeted agents in the treatment of recurrent disease. In March 2020, Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for relapsed or refractory PCNSL based on the results of the phase I/II study in Japan. Seventeen of 44 patients treated with TIR at 480 mg fasted QD, an approved dose, had overall response rate of 52.9%, median progression-free survival of 5.8 months, and time to response as short as 0.92 months. The most common adverse event at any grade was rash (32%). The skin-related disorders were manageable with appropriate skin treatments. However, greater attention and management is needed the case of more rare adverse events such as severe skin-related disorders and pneumocystis pneumonia. This lecture aims to present the recent development in treatment for PCNSL.