Scholarlink

Background <p>Third‑generation CAR-T cells demonstrated promising efficacy and remarkably low toxicity in refractory or relapsed (R/R) B-cell malignancies. However, data on the patients with central nervous system (CNS) involvement are limited due to concerns regarding treatment-related neurotoxicity. This study aimed to evaluate the safety and efficacy of a novel third-generation anti-CD19 CAR T cells in patients with CNS involvement of B-cell malignancies.</p> Methods <p>A total of 21 patients with R/R B-cell malignancies with CNS involvement, including 11 with B-cell acute lymphoblastic leukemia (B-ALL) and 10 with B-cell non-Hodgkin lymphoma (B-NHL) were enrolled. Patients derived lymphocytes were collected through apheresis and lentivirally transduced with the third-generation CAR incorporating both CD28 co-stimulation and TLR2-derived stimulatory domains (1928zT2). Patients received a single-dose 1928zT2 CAR-T cell infusion following lymphodepleting regimen. Safety, efficacy and cellular pharmacokinetics were investigated.</p> Results <p>Of the 21 patients with CNS involvement, the overall response rate (ORR) was 71% (15/21), with 73% (8/11) in B-ALL and 70% (7/10) in B-NHL. At a median follow-up of 20.4&#xa0;months, median duration of response (DOR) was 11.1&#xa0;months (95% CI, 2.9–24.4). 12-months progression-free survival (PFS) and overall survival (OS) estimates were 41.5% and 61.2%, respectively. Cytokine release syndrome (CRS) of any grade occurred in 20 patients (95%; grade ≥ 3 in 3 patients). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 9 patients (42.8%; grade ≥ 3 in 6 patients). All CRS and ICANS events were manageable. The outcomes and adverse events are comparable between B-ALL and B-NHL patients. Notably, 1928zT2 CAR-T cells demonstrated blood–brain barrier penetrance, with subsequent detection in patient cerebrospinal fluid (CSF) correlating significantly with improved clinical outcomes.</p> Conclusions <p>Third-generation 1928zT2 CAR-T cells are associated with high response rates, manageable safety and durable remissions in R/R B-cell malignancies with CNS involvement.</p> <p><i>Trial registration</i>: ClinicalTrials.gov, NCT04605666. Registered 1 May 2020.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Efficacy and safety of third-generation CD19-CAR T cells incorporating CD28 and TLR2 intracellular domains for B-cell malignancies with central nervous system involvement: results of a pivotal trial

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月27日

查看全文
  • Bailin He,
  • Ren Lin,
  • Na Xu,
  • Le Qin,
  • Zhixiang Wang,
  • Qiang Wang,
  • Xiaofang Li,
  • Xiaolei Wei,
  • Yongqiang Wei,
  • Zhaoyang Tang,
  • Zhiping Fan,
  • Fen Huang,
  • Xiaoli Liu,
  • Jing Sun,
  • Li Xuan,
  • Peng Li,
  • Hongsheng Zhou,
  • Qifa Liu

摘要

Background

Third‑generation CAR-T cells demonstrated promising efficacy and remarkably low toxicity in refractory or relapsed (R/R) B-cell malignancies. However, data on the patients with central nervous system (CNS) involvement are limited due to concerns regarding treatment-related neurotoxicity. This study aimed to evaluate the safety and efficacy of a novel third-generation anti-CD19 CAR T cells in patients with CNS involvement of B-cell malignancies.

Methods

A total of 21 patients with R/R B-cell malignancies with CNS involvement, including 11 with B-cell acute lymphoblastic leukemia (B-ALL) and 10 with B-cell non-Hodgkin lymphoma (B-NHL) were enrolled. Patients derived lymphocytes were collected through apheresis and lentivirally transduced with the third-generation CAR incorporating both CD28 co-stimulation and TLR2-derived stimulatory domains (1928zT2). Patients received a single-dose 1928zT2 CAR-T cell infusion following lymphodepleting regimen. Safety, efficacy and cellular pharmacokinetics were investigated.

Results

Of the 21 patients with CNS involvement, the overall response rate (ORR) was 71% (15/21), with 73% (8/11) in B-ALL and 70% (7/10) in B-NHL. At a median follow-up of 20.4 months, median duration of response (DOR) was 11.1 months (95% CI, 2.9–24.4). 12-months progression-free survival (PFS) and overall survival (OS) estimates were 41.5% and 61.2%, respectively. Cytokine release syndrome (CRS) of any grade occurred in 20 patients (95%; grade ≥ 3 in 3 patients). Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 9 patients (42.8%; grade ≥ 3 in 6 patients). All CRS and ICANS events were manageable. The outcomes and adverse events are comparable between B-ALL and B-NHL patients. Notably, 1928zT2 CAR-T cells demonstrated blood–brain barrier penetrance, with subsequent detection in patient cerebrospinal fluid (CSF) correlating significantly with improved clinical outcomes.

Conclusions

Third-generation 1928zT2 CAR-T cells are associated with high response rates, manageable safety and durable remissions in R/R B-cell malignancies with CNS involvement.

Trial registration: ClinicalTrials.gov, NCT04605666. Registered 1 May 2020.