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Objectives:  Secondary CNS involvement in systemic B-cell lymphoma (SCNSL) is difficult to treat and displays dismal outcome. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful treatment for systemic lymphoma. We aimed to evaluate whether CAR T-cells also represent a safe and effective therapy for SCNSL.    Methods:  We retrospectively searched our institutional database for patients with SCNSL treated with CD19-directed CAR T-cells.    Results:  We identified 10 cases, including seven patients with intra-parenchymal lesions and three patients with leptomeningeal disease. CNS staging at 1 month after CAR T-cell transfusion showed disease response (stable disease, partial response, complete response) in seven patients (70%), including two cases of long-lasting complete response (20%). One patient developed pseudoprogression which resolved under steroids. Response of CNS disease was associated with systemic 1-month response. With a median follow-up of six months, median overall and systemic progression-free survival was seven and three months, respectively. Neurotoxic symptoms occurred in six patients, with three patients developing severe neurotoxicity (≥ASTCT grade 3).    Discussion:  CAR T-cells induce considerable anti-tumor effects in SCNSL, and CNS response reflects systemic response. Neurotoxicity appears similar to previous reports on lymphoma patients without CNS involvement. CAR T-cells may therefore represent an effective and safe therapy for SCNSL.

Toxicities and Response Rates of Secondary CNS Lymphoma After Adoptive Immunotherapy With CD19-Directed Chimeric Antigen Receptor T Cells