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基于影像学的 CAR T 细胞治疗后毒性和反应模式评估。

Imaging-based Toxicity and Response Pattern Assessment Following CAR T-Cell Therapy.

机构信息

From the Department of Radiology (D.A.S., E.K., S.H.T., N.H.R.) and Department of Medicine, Division of Hematology and Oncology (P.C.), University Hospitals Cleveland Medical Center/Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106; and Blood and Marrow Transplant Program, The Ohio State University, Columbus, Ohio (M.d.L.).

出版信息

Radiology. 2022 Feb;302(2):438-445. doi: 10.1148/radiol.2021210760. Epub 2021 Nov 9.

Abstract

Background Chimeric antigen receptor (CAR) T-cell immunotherapy is increasingly used for refractory lymphoma but may lead to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Imaging may assist in clinical management. Associations between CRS or ICANS grade and imaging findings remain not fully established. Purpose To determine associations between imaging findings and clinical grade of CRS or ICANS, evaluate response patterns, and assess imaging use following CAR T-cell treatment. Materials and Methods Patients with refractory B-cell lymphoma who received CAR T-cell infusion between 2018 and 2020 at a single center were analyzed retrospectively. Clinical CRS or ICANS toxicity grade was assessed using American Society for Transplantation and Cellular Therapy, or ASTCT, consensus grading. Thoracic and head images (radiographs, CT scans, MRI scans) were evaluated. Associations between imaging findings and clinical CRS or ICANS grade were analyzed. Wilcoxon signed-rank and χ tests were used to assess associations between thoracic imaging findings, clinical CRS toxicity grade, and imaging-based response. Response to therapy was evaluated according to Deauville five-point scale criteria. Results A total of 38 patients (mean age ± standard deviation, 59 years ± 10; 23 men) who received CAR T-cell infusion were included. Of these, 24 (63% [95% CI: 48, 79]) and 11 (29% [95% CI: 14, 44]) experienced clinical grade 1 or higher CRS and ICANS, respectively. Patients with grade 2 or higher CRS were more likely to have thoracic images with abnormal findings (10 of 14 patients [71%; 95% CI: 47, 96] vs five of 24 patients [21%; 95% CI: 4, 37]; = .002) and more likely to have imaging evidence of pleural effusions (five of 14 [36%; 95% CI: 10, 62] vs two of 24 [8.3%; 95% CI: 0, 20]; = .04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; = .048). Positive imaging findings were identified in three of seven patients (43%) with grade 2 or higher ICANS who underwent neuroimaging. The best treatment response included 20 of 36 patients (56% [95% CI: 39, 72]) with complete response, seven of 36 (19% [95% CI: 6, 33]) with partial response, one of 36 (2.8% [95% CI: 0, 8]) with stable disease, and eight of 36 (22% [95% CI: 8, 36]) with progressive disease. Conclusion Thoracic imaging findings, including pleural effusions and atelectasis, correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. CAR T-cell therapy yielded high response rates. © RSNA, 2021 See also the editorial by Langer in this issue.

摘要

背景 嵌合抗原受体(CAR)T 细胞免疫疗法越来越多地用于治疗难治性淋巴瘤,但可能导致细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性综合征(ICANS)。影像学检查可能有助于临床管理。CRS 或 ICANS 分级与影像学表现之间的关联尚未完全确定。目的 确定 CRS 或 ICANS 影像学表现与临床分级之间的关联,评估反应模式,并评估 CAR T 细胞治疗后的影像学应用。材料与方法 对 2018 年至 2020 年期间在一家中心接受 CAR T 细胞输注的难治性 B 细胞淋巴瘤患者进行回顾性分析。采用美国移植与细胞治疗协会(ASTCT)共识分级标准评估临床 CRS 或 ICANS 毒性分级。评估胸部和头部影像(X 线片、CT 扫描、MRI 扫描)。分析影像学表现与临床 CRS 或 ICANS 分级之间的关系。采用 Wilcoxon 符号秩和检验和 χ 检验评估胸部影像学表现、临床 CRS 毒性分级与基于影像学的反应之间的关系。根据 Deauville 五分法标准评估治疗反应。结果 共纳入 38 例(平均年龄±标准差,59 岁±10;23 例男性)接受 CAR T 细胞输注的患者。其中,24 例(63% [95%CI:48,79%])和 11 例(29% [95%CI:14,44%])分别经历了临床 1 级或更高 CRS 和 ICANS。2 级或更高 CRS 患者更有可能出现胸部异常影像(14 例患者中有 10 例 [71%;95%CI:47,96] vs 24 例患者中有 5 例 [21%;95%CI:4,37]; =.002),更有可能出现胸腔积液(14 例患者中有 5 例 [36%;95%CI:10,62] vs 24 例患者中有 2 例 [8.3%;95%CI:0,20]; =.04)和肺不张(14 例患者中有 8 例 [57%;95%CI:30,84] vs 24 例患者中有 6 例 [25%;95%CI:7,43]; =.048)。7 例(43%)接受神经影像学检查的 2 级或更高 ICANS 患者中,有 3 例(43%)发现阳性影像学表现。最佳治疗反应包括完全缓解 20 例(56% [95%CI:39,72]),部分缓解 7 例(19% [95%CI:6,33]),稳定疾病 1 例(2.8% [95%CI:0,8]),进展疾病 8 例(22% [95%CI:8,36])。结论 CAR T 细胞输注后,胸部影像学表现,包括胸腔积液和肺不张,与细胞因子释放综合征分级相关。CAR T 细胞治疗的反应率较高。

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