OS08.8 A head-to-head comparison of two different high dose methotrexate (HDMTX) - and high dose cytarabin (HDAraC)-based chemotherapy regimens in younger patients with primary central nervous system lymphoma (PCNSL)
Authors: L. Rieger, U. Schlegel, P. Le Coutre, S. Seidel, J. Leonards, P. Martus, S. Mathas, M. Janz, A. Korfel
Journal: Neuro-Oncology (2017)

Introduction: In PCNSL, no standard therapy has been established. In younger patients, the most promising results have been achieved with HDMTX- and HDAraC- based induction chemotherapy consolidated with high-dose chemotherapy (HD) followed by autologous stem-cell transplantation (ASCT) or combined with intensive intraventricular (icv) polychemotherapy. Here, we present a head-to-head comparison of these regimens performed at two university hospitals. Materials and Methods: A total of 80 consecutive immunocompetent patients <65 years diagnosed with PCNSL (all with diffuse-large B-cell lymphoma) were treated between 2009 and 2015. The induction regimen consisted of 3 courses of Rituximab 375mg/m2 d1, HDMTX 4g/m2 d2 and Ifosfamide 800 mg/m2 d4-6 in all patients. This was to be followed by either 2 courses consolidation with HDAraC 3g/m2 d1-2 (cycles 4 and 7) and 2 courses HDMTX 4 g/m2 d1 and Ifosfamide 800 mg/m2 d3-5 (cycles 5,6), both in combination with icv polychemotherapy (MTX, AraC, Prednisolone) via an Ommaya reservoir (group A, Ruhr-University Bochum, n=43) or 2 courses HDAraC 3g/m2 d1-2 and Thiotepa 40 mg/m2 d2 followed by HD with Carmustin 3g/m2 d-5, Thiotepa 5mg/kg d -4 and -3 and ASCT d0 (group B, Charité Berlin, n=37). Patients were analysed on an intent-to-treat basis. Results: Pre-therapeutic characteristics were not significantly different in the two groups: median age was 54 years in both groups, Karnofsky Performance Status ≥70 in 30 pts (70%) in group A and 28 pts (76%) in group B, LDH elevation (>225U/l) in 14 (33%) and 17 (47%), >one lesion in 20 (47%) and 23 (62%), deep localization (basal ganglia, corpus callosum, brain stem or cerebellum) in 25 (58%) and 21 (57%), respectively. Complete therapy as planned was given to 34 patients (79%) in group A and 21 (57%) in group B. Reasons for not giving full therapy were: dislocation of Ommaya reservoir (n=2), progression on therapy (n=4), toxicity (n=2), and death on therapy (n=1) in group A and progression on therapy (n=8), death on therapy (n=2), patient`s decision (n=4) and doctor`s decision (n=2) in group B. Three patients in group A were switched to group B protocol (2 with Ommaya reservoir dislocation and one with renal failure due to HDMTX) and 2 patients in group B were switched to group A protocol (both on own demand). Complete remission was achieved in 31 patients (72%) and partial remission in 4 patients (9%) in group A (overall response rate 81%) and in 24 (65%) and 4 (11%), respectively, in group B (overall response rate 76%). The 1-year overall survival (OS) was 88.2% (SE10%) and 70.7% (SE15%), respectively (P=0.09). The 1-year progression-free survival (PFS) was 62% (SE15%) and 56.8% (SE17%) (P=0.49). Conclusions: With a relatively short follow-up, no significant difference was found for PFS and OS between the treatment groups, however, with a trend favouring the consolidation with intensive icv chemotherapy.