Primary central nervous system lymphoma (PCNSL) is a rare and aggressive non-Hodgkin’s lymphoma that affects the brain, eyes, cerebrospinal fluid, or spinal cord without systemic involvement. The outcome of patients with PCNSL is worse compared to patients with systemic diffuse large B-cell lymphoma. Given potential mortality associated with severe immune effector cell-associated neurotoxicity syndrome (ICANS), patients with PCNSL have been excluded from most clinical trials involving chimeric antigen receptor T-cell (CAR-T) therapy initially. Here, we report for the first time to apply decitabine-primed tandem CD19/CD22 dual-targeted CAR-T therapy with programmed cell death-1 (PD-1) and Bruton’s tyrosine kinase (BTK) inhibitors maintenance in one patient with multiline-resistant refractory PCNSL and the patient has maintained complete remission (CR) for a 35-month follow-up period. This case represents the first successful treatment of multiline resistant refractory PCNSL with long-term CR and without inducing ICANS under tandem CD19/CD22 bispecific CAR-T therapy followed by maintenance therapy with PD-1 and BTK inhibitors. This study shows tremendous potential in the treatment of PCNSL and offers a look toward ongoing clinical studies.
Citations
Citations to this article as recorded by
Are we ready for personalized CAR‐T therapy? Anna Strzelec, Grzegorz Helbig European Journal of Haematology.2024; 112(2): 174. CrossRef
Tislelizumab augment the efficacy of CD19/22 dual‐targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B‐cell non‐Hodgkin lymphoma Ying Zhang, Hongzhi Geng, Liangyu Zeng, Jiaqi Li, Qin Yang, Sixun Jia, Xiangping Zong, Wenzhi Cai, Shuangzhu Liu, Yutong Lu, Lei Yu, Caixia Li, Depei Wu Hematological Oncology.2024;[Epub] CrossRef
Therapeutic targeting of DNA methylation alterations in cancer Abigail V. Lee, Kevin A. Nestler, Katherine B. Chiappinelli Pharmacology & Therapeutics.2024; 258: 108640. CrossRef
Jeong Eun Lee, Dae Yong Kim, Yong Chan Ahn, Do Hoon Lim, Seung Jae Huh, Seong Soo Shin, Won Seok Kim, Won Ki Kang, Do Hyun Nam, Jung Il Lee, Jong Hyun Kim
Cancer Res Treat. 2001;33(5):398-403. Published online October 31, 2001
PURPOSE This study was performed in order to evaluate the effectiveness of combined chemotherapy and radiotherapy (RT) in primary central nervous system lymphoma (PCNSL). MATERIALS AND METHODS From January 1995 to August 1999, 21 patients with a diagnosis of PCNSL were treated with combined chemotherapy and radiotherapy. Their median age was 47 years with range of 19 to 78 years. Twelve patients were male and nine patients were female. All patients were immunocompetent and they had no evidence of systemic lymphoma. All patients underwent placement of an Ommaya reservoir and recieved a combination regimen using pre-RT systemic and intra-Ommaya methotrexate (MTX), 40 Gy whole-brain RT with a 14.4 Gy boost, and 2 courses of post-RT high-dose cytarabine. The median follow-up period of all patients and survived patients were 22 months and 36 months, respectively. RESULTS The median overall survival duration was 21 months and the overall two- and four-year survival rates were 51% and 43%, respectively. Complete response (CR), partial response, stable disease, and progressive disease were achieved in 12, 3, 1, and 5 patients, respectively. All nine patients without CR expired within 1-31 months (median 6 months). Two patients among the patients with CR developed recurrence after 13 and 14 months, respectively. The location of recurrent disease was within the port of radiation boost. Survival was influenced by age, performance status, and CR. There was one episode of MTX neurotoxicity and hepatotoxicity,respectively. CONCLUSION Combined chemotherapy and radiotherapy was an effective treatment for PCNSL, and was associated with a minimum toxicity. However, we must pay attention to the recurrence and late toxicity, particularly within two years following treatment.