Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma

Author:

Zhang Huanxin,Yan Zhiling,Wang Ying,Qi Yuekun,Hu Yongxian,Li Ping,Cao Jiang,Zhang Meng,Xiao Xia,Shi Ming,Xia Jieyun,Ma Sha,Qiao Jianlin,Li Hujun,Pan Bin,Qi Kunming,Cheng Hai,Sun Haiying,Zhu Feng,Sang Wei,Li Depeng,Li Zhenyu,Zheng Junnian,Zhao Mingfeng,Liang Aibin,Huang He,Xu Kailin

Abstract

Encouraging response has been achieved in relapsed/refractory (R/R) B-cell lymphoma treated by chimeric antigen receptor T (CAR-T) cells. The efficacy and safety of CAR-T cells in central nervous system lymphoma (CNSL) are still elusive. Here, we retrospectively analyzed 15 patients with R/R secondary CNSL receiving CD19-specific CAR-T cell-based therapy. The patients were infused with CD19, CD19/CD20 or CD19/CD22 CAR-T cells following a conditioning regimen of cyclophosphamide and fludarabine. The overall response rate was 73.3% (11/15), including 9 (60%) with complete remission (CR) and 2 (13.3%) with partial remission (PR). During a median follow-up of 12 months, the median progression-free survival (PFS) was 4 months, and the median overall survival (OS) was 9 months. Of 12 patients with systemic tumor infiltration, 7 (58.3%) achieved CR in CNS, and 5 (41.7%) achieved CR both systemically and in CNS. Median DOR for CNS and systemic disease were 8 and 4 months, respectively. At the end point of observation, of the 7 patients achieved CNS disease CR, one was still alive with sustained CR of CNS disease and systemic disease. The other 6 died of systemic progression. Of the 15 patients, 11 (73.3%) experienced grades 1-2 CRS, and no patient had grades 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 3 (20%) patients, including 1 (6.6%) with grade 4 ICANS. All the CRS or ICANS were manageable. The CD19-specific CAR-T cell-based therapy appeared to be a promising therapeutic approach in secondary CNSL, based on its antitumor effects and an acceptable side effect profile, meanwhile more strategies are needed to maintain the response.

Funder

National Natural Science Foundation of China

Publisher

Frontiers Media SA

Subject

Immunology,Immunology and Allergy

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