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CD19 导向嵌合抗原受体治疗 B 细胞急性淋巴细胞白血病的结局决定因素和进展。

Determinants of outcomes and advances in CD19-directed chimeric antigen receptor therapy for B-cell acute lymphoblastic leukemia.

机构信息

Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.

Department of Pediatric Hematology-Oncology, Mayo Clinic, Rochester, Minnesota, USA.

出版信息

Eur J Haematol. 2024 Jan;112(1):51-63. doi: 10.1111/ejh.14132.

Abstract

Relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive B-cell neoplasm associated with poor outcomes. Conventional multiagent chemotherapy and bispecific antibody therapy may induce remission; however, relapse rates remain high and overall survival is poor. Chimeric antigen receptor T-cell (CAR-T) therapy provides durable, deep complete remission, and long-term cures in relapsed and refractory B-ALL. However, with this new treatment modality, 10%-30% of patients do not achieve remission, and over 50% experience relapse after therapy. Currently, there are two approved CD19-specific CAR-T cell constructs in B-ALL, Tisagenlecleucel and Brexucabtagene Autoleucel by the United States Food and Drug Administration, and the European Medicines Agency (EMA). In this review, we discuss patients, disease, and CAR-T predictors of outcomes in B-ALL. We describe the two approved CD19-directed CAR-T cell products, review the current literature, and discuss factors associated with high risks of therapy failure and future direction in CAR-T cell therapy for B-ALL.

摘要

复发难治性 B 细胞急性淋巴细胞白血病(B-ALL)是一种侵袭性 B 细胞肿瘤,预后不良。传统的多药联合化疗和双特异性抗体治疗可能诱导缓解,但复发率仍然很高,总体生存率较差。嵌合抗原受体 T 细胞(CAR-T)治疗可为复发难治性 B-ALL 提供持久、深度完全缓解和长期治愈。然而,随着这种新的治疗方式的出现,仍有 10%-30%的患者无法缓解,并且超过 50%的患者在治疗后复发。目前,美国食品药品监督管理局(FDA)和欧洲药品管理局(EMA)批准了两种用于 B-ALL 的 CD19 特异性 CAR-T 细胞构建体,即Tisagenlecleucel 和 Brexucabtagene Autoleucel。在这篇综述中,我们讨论了 B-ALL 中患者、疾病和 CAR-T 预测结果的因素。我们描述了两种已批准的 CD19 靶向 CAR-T 细胞产品,回顾了目前的文献,并讨论了与治疗失败高风险相关的因素以及 CAR-T 细胞治疗 B-ALL 的未来方向。

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