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:Imaging-based Toxicity and Response Pattern Assessment Following CAR T-Cell Therapy.
Imaging-based Toxicity and Response Pattern Assessment Following CAR T-Cell Therapy.
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背景 嵌合抗原受体(CAR)T细胞免疫治疗越来越多地用于难治性淋巴瘤,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明确。目的 确定影像学表现与CRS或ICANS临床分级之间的关联,评估缓解模式,并评估CAR-T 细胞治疗后的影像学使用情况。材料与方法 回顾性分析2018年至2020年在单中心接受CAR-T 细胞输注的难治性B细胞淋巴瘤患者。临床CRS或ICANS毒性分级采用美国移植与细胞治疗学会(ASTCT)共识分级进行评估。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分级之间的关联。采用Wilcoxon符号秩检验和2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缓解之间的关联。根据Deauville五分法标准评估治疗缓解。结果 共纳入38例接受CAR-T 细胞输注的患者(平均年龄标准差,59岁10;23例男性)。其中,24例(63% [95% CI:48,79])和11例(29% [95% CI:14,44])分别出现临床1级或以上CRS和ICANS。
2级或以上CRS的患者胸部影像更可能出现异常表现(14例患者中10例 [71%;95% CI:47,96] vs 24例患者中5例 [21%;95% CI:4,37];P = .002)并且更可能有胸腔积液的影像学证据(14 例中 5 例 [36%;95% CI:10,62] vs 24 例中 2 例 [8.3%;95% CI:0,20];P = .04)和肺不张(14 例中 8 例 [57%;95% CI:30,84] vs 24 例中 6 例 [25%;95% CI:7,43];P = .048)。在接受神经影像学检查的 7 例 2 级或以上 ICANS 患者中,3 例(43%)发现阳性影像学表现。
最佳治疗反应包括 36 例患者中 20 例(56% [95% CI:39,72])完全缓解,36 例中 7 例(19% [95% CI:6,33])部分缓解,36 例中 1 例(2.8% [95% CI:0,8])疾病稳定,36 例中 8 例(22% [95% CI:8,36])疾病进展。结论 胸部影像学表现,包括胸腔积液和肺不张,与嵌合抗原受体(CAR)T 细胞输注后的细胞因子释放综合征分级相关。CAR-T 细胞治疗产生了较高的缓解率。RSNA,2021 本文可获取在线补充材料。另见本期 Langer 的社论。
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 2 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]; P = . 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]; P = . 04) and atelectasis (eight of 14 [57%; 95% CI: 30, 84] vs six of 24 [25%; 95% CI: 7, 43]; P = . 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 Online supplemental material is available for this article. See also the editorial by Langer in this issue.
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