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
抢先使用托珠单抗对非霍奇金淋巴瘤中 CAR-T 细胞治疗结局的影响
英文原题：Impact of Preemptive Use of Tocilizumab on Chimeric Antigen Receptor T Cell Outcomes in Non-Hodgkin Lymphoma.
查看英文原题
Impact of Preemptive Use of Tocilizumab on Chimeric Antigen Receptor T Cell Outcomes in Non-Hodgkin Lymphoma.
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中文摘要
尽管嵌合抗原受体（CAR）T细胞治疗淋巴瘤取得令人瞩目的疗效，细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS）和感染等不良事件仍是主要问题，可导致患者入住重症监护病房（ICU）甚至死亡。现行指南建议使用tocilizumab治疗2级CRS，但最佳干预时机尚未确定。本机构采用tocilizumab预防性给药策略，适用于持续1级CRS患者，定义为发热（≥38°C）超过24小时。该预防性治疗旨在减少进展为重度CRS（≥3级）、ICU入住或死亡的风险。
我们报告前瞻性连续收集的48例非霍奇金淋巴瘤患者，均接受自体CD19靶向CAR-T 治疗。共39例患者（81%）发生CRS，28例起病时为1级，另有患者起病时为2级，1例起病时为3级。34例患者接受tocilizumab，其中23例接受“预防性”tocilizumab，11例在症状出现后因2级或3级CRS接受tocilizumab。接受预防性tocilizumab的23例中，19例（83%）CRS消退且未加重；4例（17%）因发生低血压由1级进展为2级，并迅速对追加糖皮质激素应答。预防性治疗组无患者进展为3级或4级CRS。48例中10例（21%）诊断ICANS，其中5例为3级或4级。发生6起感染事件。总体ICU入住率为19%，ICANS管理是最主要入住原因（7例）；无患者因管理CRS需要入住ICU。未观察到CAR-T 毒性相关死亡。
我们的数据表明，预防性使用tocilizumab可行且有助于减少重度CRS及CRS相关ICU入住，且不影响神经毒性或感染发生率。
因此，可考虑早期使用tocilizumab，尤其适用于CRS高风险患者。
展开英文摘要原文
Despite the impressive results of chimeric antigen receptor (CAR) T cell treatment for lymphomas, adverse events such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections are major issues that can lead to intensive care unit (ICU) admission and death. Current guidelines recommend tocilizumab for treating patients with CRS grade (G) 2; however, the optimal timing of intervention has yet to be determined.
Our institution adopted the preemptive use of tocilizumab in cases of persistent G1 CRS, defined as fever ( 38 C) for >24 hours. This preemptive tocilizumab treatment aimed to reduce evolution to severe (G 3) CRS, ICU admission, or death.
We report on 48 prospectively collected consecutive patients with non-Hodgkin lymphoma treated with autologous CD19-targeted CAR T cells. In total, 39 patients (81%) developed CRS. CRS started as G1 in 28 patients, as G2 in patients, and as G3 in 1 patient. Tocilizumab was administered in 34 patients, including 23 patients who received "preemptive" tocilizumab and 11 patients who received tocilizumab for G2 or G3 CRS from the onset of symptoms.
CRS resolved without worsening severity in 19 patients out of 23 (83%) who received preemptive tocilizumab; 4 patients (17%) progressed from G1 to G2 for the development of hypotension and quickly responded to the introduction of steroids. No patients treated with a preemptive approach developed G3 or G4 CRS.
Ten out of 48 patients (21%) were diagnosed with ICANS, including 5 patients with G3 or G4. Six infectious events occurred. The overall ICU admission rate was 19%. ICANS management was the most relevant reason for ICU admission (7 patients), and no patient required ICU to manage CRS. No deaths from CAR-T toxicity were observed.
Our data indicate that preemptive tocilizumab use is feasible and useful in reducing severe CRS and CRS-related ICU admission, with no impact on neurotoxicity or infection rate.
Therefore, early use of tocilizumab can be considered, especially for patients at high risk of CRS.
论文信息
- 作者
- De Philippis C、Mannina D、Giordano L、Costantini E、Marcheselli S、Mariotti J、Sarina B、Taurino D
- 单位
- IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Rozzano, Milan, Italy. Electronic address: chiara.dephilippis@humanitas.it.Italy
- 文献类型
- 非美国政府资助研究
- 期刊
- Transplantation and cellular therapy2023 Jul
- 原文标识
- PubMed 36966874 · DOI 10.1016/j.jtct.2023.03.019