Ifosphamide and Carboplatin Based (R-DeVIC) Salvage Therapy in Patients with Relapsed/Refractory PCNSL - a Multicentre Retrospective Analysis

Background

Primary central nervous system lymphoma (PCNSL) is rare and aggressive Non-Hodgkin lymphoma of the central nervous system (CNS).High-dose methotrexate (HD-MTX) based chemotherapy is standard first-line treatment in newly diagnosed disease. Although remissions can be achieved in most patients, at least a third relapses and therapeutic options in relapsed/refractory PCNSL (r/r PCNSL) are still limited. Aim of this study was to investigate efficacy and safety in of the R-DeVIC protocol consisting of: rituximab, ifosfamide, dexamethason, carboplatin and etoposide.

Methods

This was a retrospective study based on routinely collected health data from two sites in Germany (Stuttgart and Freiburg). Patient eligibility criteria were: r/r PCNSL confirmed by local pathology treated with at least one prior therapy. The R-DeVIC protocol was applied according to the following schedule: Rituximab 375 mg/m²/d (d0), dexamethasone 40 mg/d (d1-3), etoposide 100 mg/m²/d (d1-3), ifosfamide 1500 mg/m²/d (d1-3), carboplatin 300 mg/m²/ (d1) and repeated after 21 days.

Feasibility endpoints included: toxicity, dose density, and treatment related death. Efficacy endpoints included: response as evaluated on brain MRI, progression free survival (PFS) and overall survival (OS). We used descriptive statistics for summarizing patient characteristics and outcomes; including the Kaplan-Meier estimator to plot time-to-event endpoints.

Results

We identified 19 eligible patients with r/r PCNSL being treated with R-DeVIC between 2010 and 2018. All patients received prior HD-MTX based chemotherapy (58% (11/19) treated with R-MTX/AraC/Thiotepa, 11% (2/19) treated with R-MTX/AraC and 26% (5/19) treated with R-MTX). All, but 2 patients received R-DeVIC at first progression after 1^stline treatment. In 52% (10/19), treatment was discontinued after the first cycle. In 3 patients R-DeVIC was discontinued due to severe infections or renal injury and in 2 patients due to ifosfamide induced neuro-toxicity, as well as progressive disease in 2 patients. 2 patients already achieved complete remission and in one case reasons for discontinuance were not recorded. A 2^ndcycle was administered in 47% (9/19) and 3 patients received a 3^rdcycles of R-DeVIC. Observed overall response rate after R-DeVIC was 79% (15/19): Five patients with complete and 10 with partial remission, respectively. Three (26%) patients had progressive disease and one patient achieved disease stabilization. Neutropenic fever requiring intravenous antibiotic treatment was the most common adverse event (21% of administered cycles), followed by neurological disturbances, mainly associated with ifosfamide. After a median follow-up of 5 months, 6- month and 12 -month PFS were both 47% (95% CI 24-67); 6 month and 12-month was OS 59% (95% CI 32-78).

Conclusions

R-DeVIC is a feasible therapeutic salvage option in r/r PCNSL associated with a response rate of 79%. However, substantial toxicity was also observed leading to discontinuation of treatment in about a quarter of patients. Further data will be presented at the meeting.