P14.10 Secondary CNS involvement in malignant lymphoma: Data from a multicenter prospective international registry
Authors: A. Korfel, R. Schroers, U. Schlegel, N. Schmitz, S. Hofer, O. Bairey, M. Schmidt-Hieber, A. Hirsch, P. Reimer, P. Martus
Journal: Neuro-Oncology (2017)

In systemic lymphoma, a secondary CNS involvement (secondary CNS lymphoma, SCNSL) occurs in 2-5% of patients. With conventional therapy the prognosis of SCNSL is poor with median overall survival (OS) in most series of approx. 6 months. The optimal therapeutic management has not been established; long-term control seems possible only with intensive chemotherapy including high-dose chemotherapy with autologous stem-cell transplantation (HD-ASCT). Since 2011, data on SCNSL patients have been prospectively collected in a multicenter international registry. Thus far, 173 immunocompetent patients with CNS involvement at diagnosis (cohort I, n=30) or at progression/relapse (cohort II, n=143) from 41 centers have been included. The median age was 63 years (26-86), 111 (64%) were male. The median time to CNS involvement in cohort II was 10.6 months Of 155 patients with data available, 122 (79%) had aggressive B-cell lymphoma, 25 (16%) indolent lymphoma, 5 (3%) mantle cell lymphoma and 3 (2%) T-cell lymphoma. Lymphoma localization in the CNS was brain parenchyma in 84 (54%), meningeal compartment in 37 (24%), spinal cord in 2 (1%) and a combination of these compartments in 32 (21%). Simultaneous systemic involvement was found in 42% of patients in cohort II. Therapy for CNS involvement and outcome was analyzed in 99 patients thus far (16 in cohort I and 83 in cohort II). Systemic therapy alone was given to 48 (49%), systemic + intrathecal therapy to 43 (43%), intrathecal therapy alone to 5 (5%), radiotherapy alone to 2 (2%); one patient did not receive any treatment. Systemic chemotherapy was high-dose methotrexate-based in 81 (89%) and high-dose cytarabine-based in 53 (58%); 61 (61% of all) patients received rituximab systemically. Liposomal cytarabine was the most frequent intrathecal therapy given in 30 out of 48 patients (63%). HD-ASCT was performed in 25 (25%) patients. The median progression-free survival (PFS) was 5.9 months (95% CI 3.1-8.7), the median OS 18.6 months (95% CI 10.3-26.9). On univariate analysis, CNS lymphoma at diagnosis, no meningeal involvement, better ECOG performance status, treatment with rituximab, HD-ASCT and response to therapy were associated with better outcome. Multivariate analysis was done using blockwise variable selection, starting with demographic data and findings at first diagnosis, and subsequently enlarging the model by findings at CNS involvement, therapy of CNS involvement and outcome of CNS therapy. Here, a probable prognostic role for cohort I and HD-ASCT (for OS) and no meningeal involvement (for both PFS and OS) was found with response to CNS therapy being the dominating prognostic factor (for both OS and PFS). This is the largest prospective series on SCNSL in the era of modern lymphoma therapies. The results underscore the role of intensive therapy for long-term control of SCNSL. At the meeting, an updated analysis will be presented.