CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after Failure of Chimeric Antigen Receptor T Cell Therapy (CAR-T) Therapy.
ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after Failure of Chimeric Antigen Receptor T Cell Therapy (CAR-T) Therapy.
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CAR-T 细胞疗法(CAR-T)是侵袭性复发/难治性 B 细胞淋巴瘤管理的一项重大进展;然而,复发常见且构成重大治疗挑战。不同移植和细胞治疗项目在评估和处理 CAR-T 治疗失败方面差异显著。美国移植与细胞治疗学会实践指南委员会于 2021 年 8 月至 10 月开展在线横断面调查,以了解美国淋巴瘤、移植及细胞治疗医师在检测和诊断 CAR-T 治疗失败以及管理此类弥漫大 B 细胞淋巴瘤方面的实践模式。调查邮件发送给 901 名潜在参与者,其中 174 人(19%)完成调查。应答者主要为白人(51.2%)、男性(70.7%)且执业经验超过 10 年(51.2%)。
总体而言,87% 的应答者来自大学/教学中心;54.6% 从事综合肿瘤学,45.4% 从事淋巴瘤为主的移植/细胞治疗。最常见的监测扫描时间为 CAR-T 输注后 3 个月和 12 个月。88.5% 的应答者通常或总是考虑通过活检确认复发,89% 会常规检查 CAR 靶向抗原是否持续表达(例如 CD19 CAR-T 中的 CD19)。最受欢迎的复发或进展后首个挽救方案是替代 CAR-T 疗法(双靶点或不同靶点),不论 CD19 是否阳性。对于 CD19 阳性复发,27% 的应答者选择此方案;对于 CD19 阴性复发,选择者为 31%。
总体而言,88.5% 的应答者倾向于挽救治疗应答后进行巩固性异基因造血细胞移植;51.2% 的医师会考虑对既往未接受过移植的患者进行自体造血细胞移植。各中心在 CAR-T 失败的监测、诊断和管理方面存在显著差异。亟需评估该治疗背景下新型药物的前瞻性临床试验,以确定最佳管理策略。
Chimeric antigen receptor T-cell therapy (CAR-T) is a major advance in managing aggressive relapsed or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures. The American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021 to determine the U.
S. lymphoma and transplantation and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, as well as management strategies for diffuse large B-cell lymphoma in this particular setting. E-mail surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51. 2%), male (70. 7%), and with >10 years of practice experience (51. 2%).
Overall, 87% of the responders were affiliated with university/teaching centers; 54. 6% had general oncology practices, and 45. 4% had lymphoma-focused transplantation/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion.
Overall, 88. 5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e. g. , CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. Twenty-seven percent of responders chose this regimen for CD19 positive relapse, whereas 31% of responders did so for CD19 negative relapse.
Overall, 88. 5% of responders favored consolidative allogeneic hematopoietic cell transplantation after response to salvage, whereas 51. 2% of physicians would consider autologous hematopoietic cell transplantation in transplantation-na ve patients. There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.
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