Methotrexate-cytarabine-dexamethasone combination chemotherapy with or without rituximab in patients with primary central nervous system lymphoma

// Xuefei Sun 1, * , Jing Liu 1, * , Yaming Wang 2 , Xueyan Bai 1 , Yuedan Chen 1 , Jun Qian 1 , Hong Zhu 1 , Fusheng Liu 3 , Xiaoguang Qiu 4 , Shengjun Sun 5 , Nan Ji 6 and Yuanbo Liu 1 1 Department of Hematology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 2 Department of Neurosurgery, Navy General Hospital, Beijing, China 3 Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 4 Department of Radiation Therapy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 5 Neuroimaging Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 6 Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China * These authors contributed equally to this work Correspondence to: Yuanbo Liu, email: yuanbol@ccmu.edu.cn Keywords: primary central nervous system lymphoma, rituximab, high-dose methotrexate, cytarabine, survival Received: December 21, 2016 Accepted: April 02, 2017 Published: April 13, 2017 ABSTRACT Purpose: High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). Results: The patients treated with RMAD had a complete remission rate of 66.7% after induction chemotherapy; this rate was only 33.3% in patients treated with MAD alone ( p = .011). The most common grade 1–3 adverse events were similar and included hematologic toxicity, increased aminotransferase levels, and gastrointestinal reactions. Multivariate analysis revealed that rituximab treatment was associated with longer progression-free survival (PFS, p = .005) but not overall survival (OS). Additionally, we observed that elevated serum lactate dehydrogenase was associated with shorter OS and PFS. Materials and Methods: We retrospectively analyzed 60 immunocompetent patients with newly diagnosed PCNSL at Beijing Tiantan Hospital, Capital Medical University from January 2010 to June 2016. Twenty-four patients received 3–6 courses of 3.5 g/m 2 methotrexate on day 1; 0.5–1 g/m 2 cytarabine on day 2; and 5–10 mg dexamethasone on days 1, 2 and 3. Thirty-six patients received the same combination plus rituximab 375 mg/m 2 on day 0. All patients repeated the treatment every 3 weeks. Conclusions: High-dose methotrexate based chemotherapy with rituximab yields a higher complete remission rate and does not increase serious toxicities. PFS benefits from the addition of rituximab. OS has an increasing trend in patients treated with rituximab without statistical significance.