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嵌合抗原受体 T 细胞疗法在多发性骨髓瘤中的毒性:临床试验、发病机制和管理策略经验概述。

Toxicities of Chimeric Antigen Receptor T Cell Therapy in Multiple Myeloma: An Overview of Experience From Clinical Trials, Pathophysiology, and Management Strategies.

机构信息

Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.

出版信息

Front Immunol. 2020 Dec 23;11:620312. doi: 10.3389/fimmu.2020.620312. eCollection 2020.


DOI:10.3389/fimmu.2020.620312
PMID:33424871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7793717/
Abstract

In the last few years, monoclonal antibodies (mAbs) such as elotuzumab and daratutumab have brought the treatment of multiple myeloma (MM) into the new era of immunotherapy. More recently, chimeric antigen receptor (CAR) modified T cell, a novel cellular immunotherapy, has been developed for treatment of relapsed/refractory (RR) MM, and early phase clinical trials have shown promising efficacy of CAR T cell therapy. Many patients with end stage RRMM regard CAR T cell therapy as their "last chance" and a "hope of cure". However, severe adverse events (AEs) and even toxic death related to CAR T cell therapy have been observed. The management of AEs related to CAR T cell therapy represents a new challenge, as the pathophysiology is not fully understood and there is still no well-established standard of management. With regard to CAR T cell associated toxicities in MM, in this review, we will provide an overview of experience from clinical trials, pathophysiology, and management strategies.

摘要

在过去的几年中,单克隆抗体(mAbs)如依洛珠单抗和达雷妥尤单抗将多发性骨髓瘤(MM)的治疗带入了免疫治疗的新时代。最近,嵌合抗原受体(CAR)修饰的 T 细胞,一种新型细胞免疫疗法,已被开发用于治疗复发/难治性(RR)MM,早期临床试验显示 CAR T 细胞治疗具有良好的疗效。许多晚期 RRMM 患者将 CAR T 细胞治疗视为他们的“最后机会”和“治愈的希望”。然而,已经观察到与 CAR T 细胞治疗相关的严重不良事件(AE)甚至毒性死亡。与 CAR T 细胞治疗相关的 AE 的管理代表了一个新的挑战,因为其病理生理学尚未完全了解,并且仍然没有建立良好的管理标准。关于 MM 中与 CAR T 细胞相关的毒性,在这篇综述中,我们将概述临床试验、病理生理学和管理策略方面的经验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fd/7793717/eaf989e5ea6a/fimmu-11-620312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fd/7793717/eaf989e5ea6a/fimmu-11-620312-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fd/7793717/eaf989e5ea6a/fimmu-11-620312-g001.jpg

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[3]
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[4]
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J Adv Pract Oncol. 2025-1-29

[5]
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[6]
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[7]
Updates on CAR T cell therapy in multiple myeloma.

Biomark Res. 2024-9-12

[8]
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Cancers (Basel). 2024-5-4

[9]
Exploring the efficacy and safety of anti-BCMA chimeric antigen receptor T-cell therapy for multiple myeloma: Systematic review and meta-analysis.

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[10]
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本文引用的文献

[1]
Neurotoxicity and Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy: Insights Into Mechanisms and Novel Therapies.

Front Immunol. 2020

[2]
CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions.

Front Oncol. 2020-7-28

[3]
Chimeric Antigen Receptor T Cell Therapy for Pediatric B-ALL: Narrowing the Gap Between Early and Long-Term Outcomes.

Front Immunol. 2020

[4]
How I treat adverse effects of CAR-T cell therapy.

ESMO Open. 2020-8

[5]
Clinical and radiologic correlates of neurotoxicity after axicabtagene ciloleucel in large B-cell lymphoma.

Blood Adv. 2020-8-25

[6]
Hematopoietic recovery in patients receiving chimeric antigen receptor T-cell therapy for hematologic malignancies.

Blood Adv. 2020-8-11

[7]
Clinical Predictors of Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy.

JAMA Neurol. 2020-12-1

[8]
Clinical data, limitations and perspectives on chimeric antigen receptor T-cell therapy in multiple myeloma.

Curr Opin Oncol. 2020-9

[9]
Recognizing and Grading CAR T-Cell Toxicities: An Advanced Practitioner Perspective.

Front Oncol. 2020-6-24

[10]
Macrophage, the potential key mediator in CAR-T related CRS.

Exp Hematol Oncol. 2020-7-10

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