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异基因造血细胞移植后CAR T细胞治疗后的移植物抗宿主病——通过体外光化学疗法成功治疗。

GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation - successfully treated by extracorporeal photopheresis.

作者信息

Farid Kiavasch Mohammad Nejad, Bug Gesine, Schmitt Anita, Lang Fabian, Schubert Maria-Luisa, Haberkorn Uwe, Müller-Tidow Carsten, Dreger Peter, Schmitt Michael

机构信息

Internal Medicine V, Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.

Department of Medicine 2, Hematology and Oncology, Goethe University Frankfurt, University Hospital, Frankfurt, Germany.

出版信息

Front Immunol. 2024 Nov 18;15:1500177. doi: 10.3389/fimmu.2024.1500177. eCollection 2024.

DOI:10.3389/fimmu.2024.1500177
PMID:39624098
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11609171/
Abstract

INTRODUCTION

CAR T-cell therapy is highly effective, but also associated with unique toxicities. Because of the origin of T cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined.

METHODS

Sharing our retrospective experience and a mini-review of the literature, our aim is to better understand the frequency and risk of the potential occurrence of GVHD after CAR T cells, which are most likely underestimated.

RESULTS

Here, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful long-term control of GVHD without causing relapse of the underlying disease.

DISCUSSION/CONCLUSION: In conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility, and the specific CAR construct used.

摘要

引言

嵌合抗原受体(CAR)T细胞疗法非常有效,但也伴有独特的毒性。由于CAR T细胞治疗的患者T细胞来源于先前接受过异基因造血细胞移植(alloHCT)的患者,因此CAR T细胞治疗后发生移植物抗宿主病(GVHD)成为一个相关问题,但相关研究很少。潜在的风险因素和缓解策略(从CAR T细胞修饰到临床管理)尚待确定。

方法

分享我们的回顾性经验并对文献进行简要综述,我们的目的是更好地了解CAR T细胞治疗后GVHD潜在发生的频率和风险,而这很可能被低估。

结果

在此,我们报告一组25例接受CAR T细胞治疗的同种异体移植患者中有11例出现提示GVHD的症状,其中3例(12%)的GVHD很可能是由先前的CAR T细胞治疗引发的。1例患者在接受CD19靶向CAR T细胞治疗后发生了严重的慢性肺部GVHD。体外光化学疗法(ECP)成功实现了对GVHD的长期控制,且未导致基础疾病复发。

讨论/结论:总之,CD19靶向CAR T细胞疗法在alloHCT后的患者中似乎是可行的,但可能存在引发GVHD的潜在风险,这很可能取决于T细胞来源、供体相容性以及所使用的特定CAR构建体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/fc7fce3e5a10/fimmu-15-1500177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/fde457e5d3ab/fimmu-15-1500177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/b5993ec6d5ae/fimmu-15-1500177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/fc7fce3e5a10/fimmu-15-1500177-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/fde457e5d3ab/fimmu-15-1500177-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/b5993ec6d5ae/fimmu-15-1500177-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e50a/11609171/fc7fce3e5a10/fimmu-15-1500177-g003.jpg

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