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

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/m² of MTX every 10 days (maximum three cycles). Maintenance chemotherapy of 3.5 g/m² 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.