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CD19 CAR-T 细胞治疗复发/难治性淋巴结和胃肠道滤泡性淋巴瘤:当前进展与未来展望

英文原题:CD19 CAR-T Cell Therapy for Relapsed or Refractory Nodal and Gastrointestinal Follicular Lymphoma: Current Advances and Future Perspectives.

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CD19 CAR-T Cell Therapy for Relapsed or Refractory Nodal and Gastrointestinal Follicular Lymphoma: Current Advances and Future Perspectives.

PubMed 2025/12/04(内容时间) Curr Gastroenterol Rep Q2 · IF 4.1(JCR 2025)

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研究思路按摘要原文分段

滤泡性淋巴瘤(FL)是最常见的惰性B细胞淋巴瘤,然而原发性胃肠道FL(GI-FL)仍定义不清,复发/难治性病例的治疗存在争议。本综述旨在批判性评估CD19靶向嵌合抗原受体(CAR)T细胞疗法在结直肠FL和GI-FL中的作用,重点介绍关键临床试验及GI受累的独特生物学考量。

ZUMA-5、ELARA 和 TRANSCEND FL 等关键试验已证明,在复发/难治性 FL 患者中具有较高的总缓解率和完全缓解率,以及持久的无进展生存期。尤其是 liso-cel 已显示出有利的疗效-毒性平衡,包括在转化性疾病或 24 个月内进展(POD24)的患者中。然而,针对 GI-FL 的特定数据仍然稀缺,新出现的证据表明,其微环境、免疫检查点表达和突变谱可能以不同于结内 FL 的方式影响 CAR-T 应答。CD19 CAR-T 疗法代表了复发/难治性 FL 的重大治疗进展,并为晚期或高危 GI-FL 患者带来了希望。尽管如此,GI-FL 的罕见性、专门的临床数据有限,以及治疗相关毒性、成本和可及性等挑战,仍需要进一步开展前瞻性研究。整合基于生物标志物的患者选择和 GI-FL 特异性试验设计,对于优化 CAR-T 疗法在这一独特亚型中的应用将至关重要。

展开英文摘要原文

PURPOSE OF REVIEW: Follicular lymphoma (FL) is the most common indolent B-cell lymphoma, yet primary gastrointestinal FL (GI-FL) remains poorly defined, and treatment of relapsed/refractory cases is controversial. This review aims to critically evaluate the role of CD19-directed chimeric antigen receptor (CAR) T-cell therapy in nodal and GI-FL, highlighting key clinical trials and the unique biological considerations of GI involvement.

RECENT FINDINGS: Pivotal trials such as ZUMA-5, ELARA, and TRANSCEND FL have demonstrated high overall and complete response rates with durable progression-free survival in patients with relapsed/refractory FL. Liso-cel in particular has shown a favourable efficacy-toxicity balance, including in patients with transformed disease or progression within 24 months (POD24).

However, data specific to GI-FL are scarce, and emerging evidence suggests that its microenvironment, immune checkpoint expression, and mutational profile may influence CAR-T responses differently from nodal FL. CD19 CAR-T therapy represents a major therapeutic advance for relapsed/refractory FL and holds promise for patients with advanced or high-risk GI-FL.

Nonetheless, the rarity of GI-FL, limited dedicated clinical data, and challenges such as treatment-related toxicities, costs, and accessibility warrant further prospective studies. Integrating biomarker-based patient selection and GI-FL-specific trial designs will be crucial to optimise the application of CAR-T therapy in this distinct subtype.

论文信息

作者
Watanabe T
单位
Department of Internal Medicine and Gastroenterology, Watanabe Internal Medicine, Aoyama Clinic, 1-2-21 Aoyama, Nishi-ku, Niigata-city, Japan. nabetaku@dia-net.ne.jp.Japan
文献类型
综述
期刊
Current gastroenterology reports2025 Dec 4
原文标识
PubMed 41342960 · DOI 10.1007/s11894-025-01028-9