relmacabtagene autoeucel （relma- cell）治疗成人中度至重度活动性系统性红斑狼疮的初步安全性和有效性：一项I期剂量递增研究

IF 7 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-10-01 DOI:10.1016/j.jaut.2025.103489

Yiyang Wang , Shaoying Yang , Ye Yu , Peng Xia , Cuiwei Xie , Chunyan Zhang , Liangjing Lu

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引用次数: 0

摘要

背景：嵌合抗原受体(CAR)-T细胞疗法已成为自身免疫性疾病的一种变革性治疗方法。Relmacabtagene autoeucel （relma-cel）是一种自体cd19定向CAR-T细胞产品，在中国已进入商业化阶段。这项研究评估了relma-cel治疗中度至重度活动性系统性红斑狼疮（SLE）患者的安全性和有效性。方法：在这项I期单臂剂量递增研究中，入组了8例患有中度至重度活动性SLE的女性患者。所有患者在氟达拉滨和环磷酰胺预处理后，接受逐级递增剂量（50 × 106、75 × 106或100 × 106 CAR-T细胞）的relma- cell单次输注。主要终点包括剂量限制性毒性（dlt）、不良事件（ae）和严重不良事件（sae）的发生率。次要终点包括药代动力学、药效学和疗效，通过系统性红斑狼疮疾病活动性指数2000 （SLEDAI-2K）、SLE应答者指数(SRI)-4、狼疮低疾病活动性状态（LLDAS）和SLE缓解标准中的缓解定义（DORIS）进行评估。结果：未见剂量限制性毒性反应。不良事件可控，7例患者发生细胞因子释放综合征（CRS）， 1例患者发生免疫效应细胞相关神经毒性综合征（ICANS）。患者的SLEDAI-2K平均评分从基线时的12.625分下降到随访时的3.25分。所有患者在6个月时均达到了SRI-4缓解，其中6名患者符合LLDAS标准，5名患者达到DORIS缓解。肾功能和补体水平也有所改善。结论：Relma-cel在中度至重度活动性SLE患者中具有可控的安全性和良好的疗效。根据临床反应和耐受性，100 × 106 CAR-T细胞的剂量被确定为推荐的II期剂量。

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Preliminary safety and efficacy of relmacabtagene autoleucel (relma-cel) in adults with moderately to severely active systemic lupus erythematosus: a phase I dose-escalation study

Background

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative treatment in autoimmune diseases. Relmacabtagene autoleucel (relma‐cel) is an autologous, CD19-directed CAR-T cell product developed with a commercial-ready process in China. This study evaluates the safety and efficacy of relma‐cel in patients with moderately to severely active systemic lupus erythematosus (SLE).

Methods

In this phase I, single-arm, dose escalation study, 8 female patients with moderately to severely active SLE were enrolled. All patients received a single infusion of relma‐cel at escalating doses (50 × 10⁶, 75 × 10⁶, or 100 × 10⁶ CAR-T cells) after preconditioning with fludarabine and cyclophosphamide. The primary endpoints included the incidence of dose-limiting toxicities (DLTs), adverse events (AEs), and serious adverse events (SAEs). Secondary endpoints comprised pharmacokinetics, pharmacodynamics, and efficacy, which was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), SLE Responder Index (SRI)-4, Lupus Low Disease Activity State (LLDAS), and Definition of Remission in SLE (DORIS) remission criteria.

Results

No dose-limiting toxicities were reported. Adverse events were manageable, with cytokine release syndrome (CRS) occurred in 7 patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 1 patient. The mean SLEDAI-2K score of patients decreased from 12.625 at baseline to 3.25 at follow-up. All patients achieved an SRI-4 response at 6 months, with 6 patients meeting LLDAS criteria and 5 achieving DORIS remission. Improvements in renal function and complement levels were also noted.

Conclusions

Relma-cel demonstrates a manageable safety profile and promising efficacy in patients with moderately to severely active SLE. A dose of 100 × 10⁶ CAR-T cells was identified as the recommended phase II dose based on clinical response and tolerability.

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.