AUTHOR=Li Tongjuan , Zhao Lei , Zhang Yuanyuan , Xiao Yi , Wang Di , Huang Liang , Ma Liya , Chen Liting , Liu Songya , Long Xiaolu , Meng Fankai , Zhu Xiaojian , Wei Jia , Xu Bin , Zhou Jianfeng , Zhou Xiaoxi 

TITLE=CAR T-Cell Therapy Is Effective but Not Long-Lasting in B-Cell Lymphoma of the Brain

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01306

DOI=10.3389/fonc.2020.01306

ISSN=2234-943X

ABSTRACT=Advanced central nervous system (CNS) lymphoma is an exclusion criterion for most chimeric antigen receptor (CAR) T-cell studies due to the associated levels of neurotoxicity. In this study, we described five patients with chemorefractory B-cell CNS lymphoma who received CAR19 and CAR22 T-cell “Cocktail” therapy and follow-up for 6 to 16 months. All patients experienced cytokine release syndrome (CRS). Two patients experienced CAR T-cell-related encephalopathy syndrome (CRES), which was controllable. The best response was observed in 2 patients, who successfully achieved complete remissions (CR), and the other 3 patients achieved partial remissions (PR). Four patients had progressive disease (PD) after remission. In addition, one CR patient and one PD patient accepted CAR T-cell infusion following hematopoietic stem cell transplantation therapy in the third month and were in ongoing remission for 14 and 6 months of follow-up, respectively. The targeted antigens in 2 patients were still positive, and CAR T-cells were reboosted in the cerebrospinal fluid (CSF) after PD, but a small number of CD3-positive T-cells were observed to infiltrate into the tumor. Our study indicates the efficacy of CAR T-cell therapy for CNS lymphoma with an acceptable safety profile; however, the remission did not last long, perhaps due to the tumor immunosuppressive microenvironment (TME) of the CNS. CAR T-cell therapy should be combined with other treatments to help improve the TME of cerebral lymphoma.