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

K Fritsch, B Kasenda, E Schorb, P Hau, J Bloehdorn, R Möhle, S Löw, M Binder, J Atta, U Keller, H-H Wolf, S W Krause, G Heß, R Naumann, S Sasse, C Hirt, M Lamprecht, U Martens, A Morgner, J Panse, N Frickhofen, A Röth, C Hader, M Deckert, H Fricker, G Ihorst, J Finke, G Illerhaus, K Fritsch, B Kasenda, E Schorb, P Hau, J Bloehdorn, R Möhle, S Löw, M Binder, J Atta, U Keller, H-H Wolf, S W Krause, G Heß, R Naumann, S Sasse, C Hirt, M Lamprecht, U Martens, A Morgner, J Panse, N Frickhofen, A Röth, C Hader, M Deckert, H Fricker, G Ihorst, J Finke, G Illerhaus

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.

Conflict of interest statement

SWK received travel support from Roche. UK reports personal fees from Roche, outside the submitted work. JF reports grants and personal fees from Riemser, grants and personal fees from Novartis, grants and personal fees from Neovii and grants from Medac, outside the submitted work. GH reports grants and personal fees from Roche, outside the submitted work. SK reports non-financial support from Roche, outside the submitted work. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patient flow in the PRIMAIN study.
Figure 2
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.

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