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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Siltuximab for chimeric antigen receptor T-cell therapy-related CRS and ICANS: a multicenter retrospective analysis.
Siltuximab for chimeric antigen receptor T-cell therapy-related CRS and ICANS: a multicenter retrospective analysis.
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CAR-T 细胞疗法对多种血液系统恶性肿瘤有效,但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)等不良事件会影响大量患者。发生难治性 CRS 或 ICANS 的患者治疗选择较少。Siltuximab 是一种结合循环白细胞介素 6 的单克隆抗体,已有提议认为其对 CRS 和 ICANS 均有临床活性。
我们在 6 家学术医疗中心开展多中心回顾性分析,评估真实世界队列中 CAR-T 治疗后使用 siltuximab 管理 CRS 和 ICANS 的情况,共评估 54 例患者。其中 16 例 CRS 患者此前接受过 tocilizumab,17 例 ICANS 患者此前接受过类固醇治疗。在接受 siltuximab 时仍有 CRS 的患者中,75% 的 CRS 级别改善;当时仍有 ICANS 的患者中,60% 的 ICANS 级别改善。据我们所知,这是 CAR-T 治疗后使用 siltuximab 治疗 CRS 和/或 ICANS 的最大患者队列。Siltuximab 对 CRS 和 ICANS 均显示疗效,包括既往接受过治疗的毒性。本数据支持在 CRS 和 ICANS 中使用 siltuximab,并为未来前瞻性研究提供依据。
Chimeric antigen receptor T-cell (CAR-T) therapies are effective in many hematologic malignancies; however, adverse events including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can affect a significant number of patients. Those who develop refractory CRS or ICANS have few treatment options. Siltuximab, a monoclonal antibody binding circulating interleukin-6, has been proposed to have clinical activity in both CRS and ICANS.
We conducted a multicenter retrospective analysis of siltuximab treatment for CRS and ICANS after CAR-T therapy in a real-world cohort from 6 academic centers. Fifty-four patients were evaluated. Sixteen patients had CRS previously treated with tocilizumab and 17 patients had ICANS previously treated with steroids. Of the patients with CRS at the time of siltuximab, 75% had improvement in CRS grade.
Of the patients with ICANS at the time of siltuximab, 60% had improvement in ICANS grade. To our knowledge, this is the largest cohort of patients treated with siltuximab for CRS and/or ICANS after CAR-T therapies. Siltuximab appeared to be effective for both CRS and ICANS, including previously treated toxicities. These data support the use of siltuximab in CRS and ICANS as well as provide rationale for future prospective studies.
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