The MATRix regimen (methotrexate, cytarabine, thiotepa, rituximab) may be the new standard chemoimmunotherapy for the treatment of patients aged up to 70 years with newly diagnosed primary central nervous system (CNS) lymphoma, a study published in the journal The Lancet Haematology has suggested.1

Because active therapies for primary CNS lymphoma are often associated with an elevated risk of hematologic or neurologic toxicity, a standard approach remains undefined. Therefore, researchers sought to evaluate the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate and cytarabine, followed by consolidation whole-brain radiotherapy or autologous hematopoietic cell transplantation (HCT).

For the international phase 2 trial, researchers enrolled 227 HIV-negative patients with newly diagnosed primary CNS lymphoma from 53 centers in Europe. Participants were randomly assigned 1:1:1 to receive 4 courses of methotrexate 3.5 g/m2 on day 1 plus cytarabine 2 g/m2 twice daily on days 2 and 3; or the same combination plus 2 doses of rituximab 375 mg/m2 on days −5 and 0; or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m2 on day 4. All 3 arms repeated treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated to receive whole-brain radiotherapy or autologous HCT.

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Results showed that at a median follow-up of 30 months, patients who receive the MATRix combination had a complete remission rate of 49% (95% CI, 38 – 60), compared with 23% (95% CI, 14 – 31) of patients treated with methotrexate plus cytarabine alone (HR, 0.46; 95% CI, 0.28 – 0.74) and 30% of those treated with methotrexate plus cytarabine and rituximab (HR, 0.61; 95% CI, 0.40 – 0.94).

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In terms of safety, patients treated with MATRix more frequently experienced grade 4 hematologic toxicity; however, the rate of infective complications was similar among 3 cohorts.

The most common grade 3 or 4 adverse events in all 3 treatment arms were neutropenia, thrombocytopenia, anemia, and febrile neutropenia or infection. Of note, 13 patients died due to treatment-related toxicity.


  1. Ferreri AJM, Cwynarski K, Pulczynski E, et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial [published online ahead of print April 6, 2016]. Lancet Haematol. doi: 10.1016/S2352-3026(16)00036-3.