嵌合抗原受体 T 细胞 CD19 在二线大 B 细胞淋巴瘤中的作用:来自 3 期临床试验的经验教训。美国移植和细胞治疗学会专家小组意见。
Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy.
机构信息
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York.
Hematologic Malignancies, Transplantation, and Cellular Therapy Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas.
出版信息
Transplant Cell Ther. 2022 Sep;28(9):546-559. doi: 10.1016/j.jtct.2022.06.019. Epub 2022 Jun 26.
Since 2017, 3 CD19-directed chimeric antigen receptor (CAR) T cell therapies-axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel-have been approved for relapsed/refractory aggressive diffuse large B cell lymphoma after 2 lines of therapy. Recently, 3 prospective phase 3 randomized clinical trials were conducted to define the optimal second-line treatment by comparing each of the CAR T cell products to the current standard of care: ZUMA-7 for axicabtagene ciloleucel, BELINDA for tisagenlecleucel, and TRANSFORM for lisocabtagene maraleucel. These 3 studies, although largely addressing the same question, had different outcomes, with ZUMA-7 and TRANSFORM demonstrating significant improvement with CD19 CAR T cells in second-line therapy compared with standard of care but BELINDA not showing any benefit. The US Food and Drug Administration has now approved axicabtagene ciloleucel and lisocabtagene maraleucel for LBCL that is refractory to first-line chemoimmunotherapy or relapse occurring within 12 months of first-line chemoimmunotherapy. Following the reporting of these practice changing studies, here a group of experts convened by the American Society for Transplantation and Cellular Therapy provides a comprehensive review of the 3 studies, emphasizing potential differences, and shares perspectives on what these results mean to clinical practice in this new era of treatment of B cell lymphomas.
自 2017 年以来,已有 3 种靶向 CD19 的嵌合抗原受体(CAR)T 细胞疗法——axicabtagene ciloleucel、tisagenlecleucel 和 lisocabtagene maraleucel——获批用于二线治疗 2 线治疗后复发/难治性侵袭性弥漫性大 B 细胞淋巴瘤。最近,进行了 3 项前瞻性 3 期随机临床试验,通过将每种 CAR T 细胞产品与当前的标准护理进行比较,来确定最佳的二线治疗方法:ZUMA-7 用于 axicabtagene ciloleucel、BELINDA 用于 tisagenlecleucel 和 TRANSFORM 用于 lisocabtagene maraleucel。这 3 项研究虽然主要解决了同一个问题,但结果却有所不同,ZUMA-7 和 TRANSFORM 研究表明,与标准护理相比,CD19 CAR T 细胞在二线治疗中显著改善,而 BELINDA 研究则未显示出任何获益。美国食品和药物管理局现已批准 axicabtagene ciloleucel 和 lisocabtagene maraleucel 用于一线化疗免疫治疗耐药或一线化疗免疫治疗后 12 个月内复发的弥漫性大 B 细胞淋巴瘤。在这些改变实践的研究报告后,美国移植和细胞治疗学会的一组专家对这 3 项研究进行了全面回顾,强调了潜在的差异,并就这些结果在治疗弥漫性大 B 细胞淋巴瘤的新时代对临床实践意味着什么分享了观点。