HDMTX-based Induction Therapy Followed by Consolidation with Conventional Systemic Chemotherapy and Intraventricular Therapy (modified Bonn Protocol) in Primary CNS Lymphoma: a Monocentric Retrospective Analysis

Background: To evaluate outcome and toxicity of High-dose methotrexate (HDMTX)-based induction therapy followed by consolidation with conventional systemic chemotherapy and facultative intraventricular therapy (modified Bonn protocol) in patients with primary CNS lymphoma (PCNSL).

Methods: Between 01/2005 and 12/2013 113 patients with newly diagnosed PCNSL presented at our center; 98 of those qualified for HDMTX based chemotherapy, received a modified Bonn protocol and were included in the analysis. The treatment regimen was based on the "Bonn protocol", but modified by omission of systemic drugs not able to cross the intact blood brain barrier. Intraventricular therapy was postponed until completion of three induction chemotherapy cycles or was replaced by intrathecal liposomal AraC and rituximab was added to induction from 2010 onwards.

Results: Median patient age was 67 years (range 38-83). Complete response/complete response unconfirmed (CR/CRu) was achieved in 59/98 patients (60%), partial response (PR) in 9/98 patients (9%). Twenty-four patients (23%) had progressive disease (PD), 6 (6%) died on therapy. Median progression-free survival (PFS) for all patients was 11.4 months, median overall survival (OS) 29.1 months. A trend to better outcome for intraventricular therapy versus intrathecal liposomal AraC was found in patients < 65 years (HR 0.53 [0.19-1.47] for OS and 0.46 [0.21-1.02] for PFS. Ommaya reservoir infection occurred in 3/33 patients (9%).

Conclusions: The data of this single center experience suggest that the outcome with a modified Bonn protocol was comparable to that of the previous regimen, showed fewer Ommaya reservoir infections and may have a trend for better outcome with intraventricular therapy.