Immuno-Chemotherapy with Rituximab, Methotrexate, Lomustine, and Procarbazine for the Treatment of Primary CNS Lymphoma in Patients >65 Years.

Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) confined to the CNS and/or eyes at presentation. PCNSL have a poor prognosis dispite good initial response to steroids and whole brain irradiation (WBRT). Addition of high-dose methotrexate (MTX) to therapy has improved the prognosis of patients with PCNSL, resulting in median survival rates of up to 60 months (mo). However, most patients eventually relapse. Surviving patients, particularly elderly treated with combined radio-chemotherapy are at substantial risk of developing leukoencephalopathy. We developed a protocol with high-dose MTX combined with the lipophilic alkylating agents procarbacine and lomustine and the anti-CD20 monoclonal antibody rituximab (R-MPL protocol), especially adapted for elderly patients with PCNSL. Here we report the results of 28 patients treated with combined immuno-chemotherapy with R-MPL protocol within a monocentric study.

Patients ≥65 yrs with PCNSL were treated with up to 3 cycles of R-MPL protocol: rituximab (375mg/m² d-6, 1, 15, 29), MTX (3g/m² d2, 16, 30), procarbazine (60 mg/m² p.o., d1-10) and lomustine (110 mg/m² p.o., d1). Cycles were repeated d42. Inclusion criterias were age ≥65 yrs and biopsy proven PCNSL. There was no lower limit of Karnofsky Performance Score.

28 patients (median age 75 yrs., range 65-83 yrs.) received R-MPL protocol. 2 patients died, one due to pulmonary embolism 2 weeks after initiation of treatment, the other had a perforation of the sigmoid and both were not evaluable for response. Objective response was seen in 25 of 26 patients (96,2%) with 19 CR and 6 PR. In 5 patients, MTX was not tolerated after 1 (n=4) and 2 (n=1) applications due to cholestatic hepatitis (n=1) and renal impairment (n=4). 2 patients with refractory disease could successfully be salvaged with AraC/thiotepa (n=1) and HDT and ASCT (n=1), respectively. 5 patients experienced relapse and could not be salvaged. After a median follow-up of 26 mo (range 2-35) 10 patients (35,7 %) are alive and disease-free. By intend-to-treat-analysis the 12-mo and 24-mo is 69% and 52% respectively. Severe leukoencephalopathy has not been observed. Most recent follow-up data will be presented in detail.

The immuno-chemotherapy protocol presented here is safe and shows high efficacy in treating elderly patients with PCNSL. A prospective phase-II trial will be initiated.

No relevant conflicts of interest to declare.