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静脉注射免疫球蛋白用于治疗与嵌合抗原受体T细胞(CAR-T)疗法相关的严重神经毒性患者。

Intravenous Immunoglobulin (IVIG) for Patients with Severe Neurotoxicity Associated with Chimeric Antigen Receptor T-Cell (CAR-T) Therapy.

作者信息

Mokhtari Sepideh, Asquith Justin M, Kareem Syeda Saba, Bachmeier Christina A, Pina Yolanda, Faramand Rawan G, Kim Youngchul, Peguero Edwin N, Sahebjam Solmaz, Jaffer Mohammad H, Iacono David P, Jain Michael D, Vogelbaum Michael A, Davila Marco L, Forsyth Peter A, Locke Frederick L, Lazaryan Aleksandr

机构信息

Department of Neuro-Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.

Department of Medical Oncology, Aspirus Cancer Care, Wausau, WI 54401, USA.

出版信息

Int J Mol Sci. 2025 Apr 21;26(8):3904. doi: 10.3390/ijms26083904.


DOI:10.3390/ijms26083904
PMID:40332772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12028060/
Abstract

Severe immune effector cell-associated neurotoxicity syndrome (ICANS) occurs in about 30% of all patients with large B-cell lymphoma (LBCL) who are treated with axicabtagene ciloleucel (axi-cel). There are currently limited treatment strategies other than the standard corticosteroids, and it is essential to find additional therapies to manage severe ICANS. We conducted a retrospective study of neurologic outcomes among patients who received axi-cel for LBCL from May 2015 to February 2019. We identified patients who developed severe ICANS and were treated with glucocorticoids followed by intravenous immunoglobulin (IVIG) (n  =  9) or glucocorticoids alone (n  =  10). There was no statistically significant difference in the time to resolution (TTR) of severe ICANS between groups; however, patients in the IVIG had more severe grades of ICANS with a lower performance status at baseline. The cumulative steroid days were 11.2 in the IVIG arm and 13.5 in the glucocorticoids-only arm. The use of IVIG for severe ICANS after axi-cel therapy was tolerable and safe and is generally recommended in the CAR-T setting in patients with hypogammaglobinemia. The use of IVIG as a potential therapeutic agent for severe ICANS can be further explored in future prospective studies.

摘要

严重免疫效应细胞相关神经毒性综合征(ICANS)发生在约30%接受axi-cel(阿基仑赛注射液)治疗的大B细胞淋巴瘤(LBCL)患者中。除了标准的皮质类固醇外,目前治疗策略有限,因此找到额外的疗法来治疗严重的ICANS至关重要。我们对2015年5月至2019年2月期间接受axi-cel治疗LBCL的患者的神经学结局进行了一项回顾性研究。我们确定了发生严重ICANS并接受糖皮质激素治疗随后接受静脉注射免疫球蛋白(IVIG)的患者(n = 9)或仅接受糖皮质激素治疗的患者(n = 10)。两组之间严重ICANS的缓解时间(TTR)没有统计学上的显著差异;然而,接受IVIG治疗的患者ICANS分级更严重,基线时体能状态更低。IVIG组的累积类固醇使用天数为11.2天,仅使用糖皮质激素组为13.5天。axi-cel治疗后使用IVIG治疗严重ICANS是可耐受且安全的,在低丙种球蛋白血症的CAR-T治疗环境中通常推荐使用。IVIG作为严重ICANS的潜在治疗药物的应用可在未来的前瞻性研究中进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/0bde418f19a5/ijms-26-03904-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/e54c87105855/ijms-26-03904-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/edd94cc723a2/ijms-26-03904-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/0bde418f19a5/ijms-26-03904-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/e54c87105855/ijms-26-03904-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/edd94cc723a2/ijms-26-03904-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a3/12028060/0bde418f19a5/ijms-26-03904-g003.jpg

相似文献

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Intravenous Immunoglobulin (IVIG) for Patients with Severe Neurotoxicity Associated with Chimeric Antigen Receptor T-Cell (CAR-T) Therapy.

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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma.

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[9]
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[10]
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本文引用的文献

[1]
Single-center experience using anakinra for steroid-refractory immune effector cell-associated neurotoxicity syndrome (ICANS).

J Immunother Cancer. 2022-1

[2]
Management of Immune-Related Adverse Events in Patients Treated With Chimeric Antigen Receptor T-Cell Therapy: ASCO Guideline.

J Clin Oncol. 2021-12-10

[3]
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events.

J Immunother Cancer. 2020-12

[4]
Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel.

Clin Cancer Res. 2020-9-15

[5]
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Am Soc Clin Oncol Educ Book. 2019-1

[6]
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Biol Blood Marrow Transplant. 2018-12-25

[7]
Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial.

Lancet Oncol. 2018-12-2

[8]
Use of intravenous immunoglobulin for the treatment of autoimmune encephalitis: audit of the NHS experience.

JRSM Open. 2018-9-3

[9]
Clinical and Biological Correlates of Neurotoxicity Associated with CAR T-cell Therapy in Patients with B-cell Acute Lymphoblastic Leukemia.

Cancer Discov. 2018-6-7

[10]
IVIg Promote Cross-Tolerance against Inflammatory Stimuli In Vitro and In Vivo.

J Immunol. 2018-5-9

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