BIOM-65. NEW BIOMARKERS FOR THE DIAGNOSIS OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN CEREBROSPINAL FLUID: AN EXPLORATORY MULTICENTER RETROSPECTIVE COHORT STUDY

Abstract

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma which may be treated with curative intent. Diagnosis often requires a brain biopsy, which is associated with complications and delay of diagnosis. Cerebrospinal fluid (CSF) analysis can currently provide a diagnosis (without the need for a biopsy) in only a minority of PCNSL patients. The aim of this study is to identify new potential biomarkers in CSF for patients with clinical suspicion of PCNSL, to improve the diagnostic yield of CSF analysis. METHODS CSF samples were analyzed from a retrospective cohort that included patients with clinical suspicion of PCNSL at two Dutch hospitals between August 2020 and October 2021. First-step analysis consisted of targeted multiplex biomarker analysis using a proximity extension assay (Olink), allowing the simultaneous analysis (relative expression levels) of 184 protein markers in a small CSF volume. To validate the discovered biomarkers in a quantitative manner, a second analysis was performed in a subgroup of patients with a bead-based multiplex immune-assay (Luminex). RESULTS A total of 76 patients were included, of whom 11 patients (14%) were diagnosed with PCNSL. The mean age was 62 years (range 22-83 years), and 62% of the patients were male. In the primary analysis, 31 markers showed significant differences (p< 0.05) between PCNSL patients and controls. After correction for multiple testing, 6 markers remained significant, including the known chemokine marker CXCL13, as well as new markers. The quantitative analysis confirmed significant differences (p< 0.05) for 3 markers: CXCL10, programmed cell death protein 1 (PDCD1) and FAS natural ligand (FASLG). CONCLUSION We identified a novel panel of potential diagnostic markers in CSF for the diagnosis of PCNSL. The diagnostic value of these markers will be validated in an ongoing multicenter prospective study.