Frontiers in Immunology (Aug 2022)
Efficacy and safety of CD19-specific CAR-T cell-based therapy in secondary central nervous system lymphoma
- Huanxin Zhang,
- Huanxin Zhang,
- Zhiling Yan,
- Zhiling Yan,
- Ying Wang,
- Ying Wang,
- Yuekun Qi,
- Yuekun Qi,
- Yongxian Hu,
- Ping Li,
- Jiang Cao,
- Jiang Cao,
- Meng Zhang,
- Xia Xiao,
- Ming Shi,
- Ming Shi,
- Jieyun Xia,
- Jieyun Xia,
- Sha Ma,
- Sha Ma,
- Jianlin Qiao,
- Jianlin Qiao,
- Hujun Li,
- Hujun Li,
- Bin Pan,
- Bin Pan,
- Kunming Qi,
- Kunming Qi,
- Hai Cheng,
- Hai Cheng,
- Haiying Sun,
- Haiying Sun,
- Feng Zhu,
- Feng Zhu,
- Wei Sang,
- Wei Sang,
- Depeng Li,
- Depeng Li,
- Zhenyu Li,
- Zhenyu Li,
- Junnian Zheng,
- Junnian Zheng,
- Mingfeng Zhao,
- Aibin Liang,
- He Huang,
- Kailin Xu,
- Kailin Xu
Affiliations
- Huanxin Zhang
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Huanxin Zhang
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Zhiling Yan
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Zhiling Yan
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Ying Wang
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Ying Wang
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Yuekun Qi
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Yuekun Qi
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Yongxian Hu
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Ping Li
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
- Jiang Cao
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jiang Cao
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Meng Zhang
- Department of hematology, Tianjin First Central Hospital, Tianjin, China
- Xia Xiao
- Department of hematology, Tianjin First Central Hospital, Tianjin, China
- Ming Shi
- Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Ming Shi
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jieyun Xia
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jieyun Xia
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Sha Ma
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Sha Ma
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Jianlin Qiao
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Jianlin Qiao
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Hujun Li
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Hujun Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Bin Pan
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Bin Pan
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Kunming Qi
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Kunming Qi
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Hai Cheng
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Hai Cheng
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Haiying Sun
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Haiying Sun
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Feng Zhu
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Feng Zhu
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Wei Sang
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Wei Sang
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Depeng Li
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Depeng Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Zhenyu Li
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Zhenyu Li
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- Junnian Zheng
- Cancer Institute, Xuzhou Medical University, Xuzhou, China
- Junnian Zheng
- Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Mingfeng Zhao
- Department of hematology, Tianjin First Central Hospital, Tianjin, China
- Aibin Liang
- Department of Hematology, Tongji Hospital of Tongji University, Shanghai, China
- He Huang
- Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Kailin Xu
- Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
- Kailin Xu
- Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China
- DOI
- https://doi.org/10.3389/fimmu.2022.965224
- Journal volume & issue
-
Vol. 13
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.
Keywords
- secondary central nervous system lymphoma
- chimeric antigen receptor t cell
- relapsed/refractory
- immunotherapy
- immune effector cell-associated neurotoxicity syndrome
