High‐dose methotrexate monotherapy for newly diagnosed primary central nervous system lymphoma: 15‐year multicenter experience

Abstract Aim Primary central nervous system lymphoma (PCNSL) is rare disease and shows poor prognosis although methotrexate‐based chemotherapy is used. Here, we present our experiences with high‐dose methotrexate (HD‐MTX) monotherapy for immunocompetent patients with PCNSL at three institutions and investigate factors related to survival. Methods PCNSL patients, who were histologically confirmed with diffuse large B cells and treated with HD‐MTX monotherapy from 2001 to 2016, were retrospectively reviewed. Patients underwent induction chemotherapy with 8 g/m 2 of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m 2 of MTX (maximum six cycles) was selectively performed depending on the response to induction chemotherapy. Results A total of 67 patients were included. Although seven patients discontinued induction chemotherapy because of MTX toxicity, 40 (59.7%) patients showed a complete response (CR) to induction chemotherapy. Twenty‐six (38.8%) and three (4.5%) patients showed a CR and partial response, respectively, after maintenance chemotherapy. Forty‐one patients with recurrence or progression following HD‐MTX underwent second‐line treatment. Progression‐free survival rates were 43% and 24% at 1 and 2 years, respectively. The median overall survival was 40.3 months. In a multivariate analysis, a radiological CR to induction chemotherapy was a significant factor related to prolonged progression‐free survival and overall survival ( P < 0.05). Conclusion MTX‐monotherapy is tolerable in terms of adverse effects and still considered as a treatment option in patients with PCNSL. However, an additional therapeutic option should be prepared for non‐CR responders to induction chemotherapy.