Online First

Case Report
A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells
Ken Takigawa1,2, Noriaki Kawano1, Yasuo Mori2, Takuji Yamauchi2, Taro Tochigi1, Kohta Miyawaki2, Kyohei Mori2, Masatoshi Shimo2, Takashi Nakaike1, Kiyoshi Yamashita1, Koichi Mashiba1, Ikuo Kikuchi1, Kousuke Marutsuka3, Koichi Ohshima4, Koji Kato2, Koichi Akashi2

1 Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan

2 Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Science, Fukuoka, Japan

3 Department of Pathology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan

4 Department of Pathology, Kurume University, Fukuoka, Japan

CNS lymphoma, CAR-T cell therapy, dynamics of CAR-T cells in PB, CRS, ICANS
Submitted:October 27, 2023
Accepted:January 4, 2024
Published online:March 29, 2024


Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/μL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events ― cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.



Online ISSN:2432-7026