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
B 细胞淋巴瘤中 CD19 CAR-T 治疗后的细胞因子释放综合征与神经毒性
英文原题：Cytokine Release Syndrome and Neurotoxicity Following CD19 CAR-T in B-Cell Lymphoma.
查看英文原题
Cytokine Release Syndrome and Neurotoxicity Following CD19 CAR-T in B-Cell Lymphoma.
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中文摘要
CAR-T 细胞疗法可有效治疗复发/难治性大B细胞淋巴瘤（LBCL），但毒性仍令人担忧，尤其是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）。
本研究分析这些毒性的时间趋势、危险因素及其严重程度之间的关联。在国际血液与骨髓移植研究中心的登记研究中，分析了2018至2020年间接受商业化CAR-T 治疗的1916例LBCL患者（阿基仑赛占74.9%，替沙妥仑赛占25.1%）。结局包括CRS/ICANS发生、依据ASTCT标准确定的发生时间和严重程度，以及总生存期（OS）；采用Cox比例风险模型评估危险因素。发生CRS的患者占75.2%，其中11.3%为3级；发生ICANS的患者占43.5%，其中47.7%为3级。CRS患者中的重度CRS比例从2018年的14.0%降至2020年的9.2%（P<.01）；但ICANS患者中的重度ICANS比例无统计学变化（2018年41.5%，2020年53.7%，P=.10）。
CRS与ICANS相关：发生CRS患者中57.1%也出现ICANS，而ICANS病例中97.5%报告CRS，提示两种毒性可能构成连续过程。阿基仑赛与发生任何级别CRS（OR 4.6，95% CI 3.65–5.81）和ICANS（OR 5.85，95% CI 4.48–7.64）的风险较高相关，也与两种并发症的早发和重症形式相关。年龄较大、体能状态较差及输注前乳酸脱氢酶升高也可不同程度预测这些毒性。从输注后第30天开始的里程碑分析显示，发生重度CRS或ICANS患者OS短于未发生者。重度CRS随时间改善可能与更早干预有关，而ICANS的发生与CRS本身密切相关。结果强调了有效减轻这些毒性、提高CAR-T 安全性的必要性。
展开英文摘要原文
Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL).
However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.
9%, tisagenlecleucel 25. 1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk factors were assessed using Cox proportional hazards model. Among patients developing CRS (75. 2%), 11. 3% had grade 3 CRS. Among patients developing ICANS (43. 5%), 47. 7% had grade 3 ICANS. Among patients developing CRS, severe CRS rates decreased from 14. 0% in 2018 to 9. 2% in 2020 (P< . 01).
However, the proportion of severe ICANS in patients who developed ICANS remained statistically unchanged (41. 5% in 2018 to 53. 7% in 2020, P= . 10). CRS and ICANS were correlated: 57. 1% of patients with CRS also experienced ICANS, and CRS was reported in 97. 5% of ICANS cases, suggesting a potential continuum between toxicities. Axicabtagene ciloleucel was associated with higher risk of any grade CRS (OR, 4. 6; 95% CI, 3. 65 to 5. 81) and ICANS (OR, 5. 85; 95% CI, 4. 48 to 7.
64) as well as early and severe forms of both complications. Older age, lower performance status, and elevated lactate dehydrogenase levels prior to infusion also variably predicted these toxicities. In a landmark analysis starting 30 days postinfusion, patients with severe CRS or severe ICANS had shorter OS compared to those without these toxicities. High grades of CRS improved over time likely related to earlier intervention, development of ICANS is intrinsically related with CRS.
These findings underscore the need for effective strategies to mitigate these toxicities and improve CAR-T safety.
论文信息
- 作者
- Shouval R、Strouse C、Kim S、Oloyede T、Ahmed S、Awan FT、Luan D、Bachanova V
- 第一作者单位
- Adult BMT Service, Memorial Sloan Kettering Cancer Center, New York, New York; Weill Cornell Medicine, New York, New York.United States
- 通讯作者单位
- CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: mpasquini@mcw.edu.United States
- 期刊
- Transplantation and cellular therapy2025 Jul
- 原文标识
- PubMed 40288610 · DOI 10.1016/j.jtct.2025.03.011
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