High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

Abstract

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m², days 1, 15, 29), high-dose methotrexate (3 g/m² days 2, 16, 30), procarbazine (60 mg/m² days 2-11) and lomustine (110 mg/m², day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Trial registration: ClinicalTrials.gov NCT00989352.

Figure 1

Patient flow in the PRIMAIN study.

Figure 2

Survival analyses. (a) PFS of the entire cohort, (b) OS of the entire cohort, (c) PFS stratified by R-MPL, (d) OS stratified by R-MPL, (e) cumulative incidence of death owing to lymphoma with other causes of death as competing risk and (f) cumulative incidence of death owing to other causes but lymphoma with lymphoma-associated death as competing risk.