Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, Ohio.
Curr Probl Cancer. 2022 Feb;46(1):100826. doi: 10.1016/j.currproblcancer.2021.100826. Epub 2021 Dec 25.
Chimeric antigen receptor-modified (CAR) T-cell therapy targeting CD19 has revolutionized the treatment of relapsed or refractory B-cell lymphomas. Based on unprecedented response rates and durability of response in high risk B-cell lymphoma patients, anti-CD19 CAR T-cell therapy was rapidly approved by the FDA for a variety of lymphoma subtypes. Anti-CD19 CAR T-cell therapy is now considered standard of care for patients with relapsed or refractory (R/R) aggressive non-Hodgkin's Lymphoma (NHL) after 2 or more lines of therapy. Three second-generation anti-CD19 CAR T-cell products have been FDA approved for R/R aggressive B-cell lymphoma and FDA approval has been obtained for Mantle Cell Lymphoma and Follicular lymphoma as well. This has ensured broad access to CAR T-cell therapy for patients with NHL and new real-world trials have helped confirm feasibility of CAR T-cell therapy for a broad patient population. The emergence of CAR T-cell therapy will likely provide a new patient population who is status post anti-CD19 CAR T-cell therapy. Investigation of mechanisms of failure of CAR T-cell therapy and clinical trials to study strategies to address this are thus required. Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation to address this.
嵌合抗原受体修饰 (CAR) T 细胞疗法靶向 CD19 已经彻底改变了复发或难治性 B 细胞淋巴瘤的治疗方法。基于高危 B 细胞淋巴瘤患者前所未有的反应率和反应持久性，抗 CD19 CAR T 细胞疗法已迅速被 FDA 批准用于多种淋巴瘤亚型。抗 CD19 CAR T 细胞疗法现在被认为是二线或以上治疗后复发或难治性（R/R）侵袭性非霍奇金淋巴瘤（NHL）患者的标准治疗方法。三种第二代抗 CD19 CAR T 细胞产品已获得 FDA 批准用于 R/R 侵袭性 B 细胞淋巴瘤，并且也已获得 FDA 批准用于套细胞淋巴瘤和滤泡性淋巴瘤。这确保了广泛的 CAR T 细胞疗法可用于 NHL 患者，并且新的真实世界试验有助于确认 CAR T 细胞疗法对广泛患者群体的可行性。CAR T 细胞疗法的出现可能为接受过抗 CD19 CAR T 细胞治疗的患者提供新的治疗选择。因此，需要研究 CAR T 细胞治疗失败的机制，并开展临床试验以研究解决这些问题的策略。在这里，我们全面回顾了 FDA 批准的抗 CD19 CAR T 细胞产品 axicabtagene ciloleucel、tisagenlecleucel 和 lisocabtagene maraleucel 在惰性或侵袭性 B 细胞淋巴瘤患者中的应用，并讨论了 CAR T 细胞治疗失败的机制以及目前正在研究的潜在方法来解决这些问题。
