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一个新的交集:西米普利单抗和替利莫基因拉赫帕里韦克治疗晚期皮肤鳞状细胞癌患者后发生的巨细胞病毒性胃炎

A Novel Intersection: Cytomegalovirus Gastritis Following Cemiplimab and Talimogene Laherparepvec in a Patient With Advanced Cutaneous Squamous Cell Carcinoma.

作者信息

Egoryan Goar, Zimmet Alex, Yu Mingwei, Pozdol Joseph, Subramanian Aruna, Reddy Sunil, Nelson Joanna

机构信息

Division of Oncology, Department of Medicine Stanford University School of Medicine Stanford California USA.

Department of Pathology Stanford University School of Medicine Stanford California USA.

出版信息

Clin Case Rep. 2024 Dec 15;12(12):e9632. doi: 10.1002/ccr3.9632. eCollection 2024 Dec.

DOI:10.1002/ccr3.9632
PMID:39687659
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11646813/
Abstract

Cytomegalovirus (CMV) reactivation is a rare complication in patients treated with immune checkpoint inhibitors (ICIs), typically occurring after immunosuppressive therapy for immune-related adverse events (irAEs). Here, we report a unique case of severe CMV gastritis in a patient receiving cemiplimab, an anti-PD-1 antibody, and talimogene laherparepvec (T-VEC), an oncolytic virus, without prior irAEs or immunosuppressive treatment. A 63-year-old man with advanced cutaneous squamous cell carcinoma received cemiplimab for one year and a single T-VEC injection for recurrent disease. He presented with progressive dyspepsia, significant weight loss, and malnutrition requiring total parenteral nutrition. Endoscopy revealed extensive gastric ulceration, and biopsies confirmed CMV gastritis. Initial treatment with intravenous ganciclovir improved his viral load but provided minimal symptomatic relief. After six weeks of therapy, biopsies showed resolution of CMV infection, and the patient transitioned to oral valganciclovir for prophylaxis while resuming cancer treatment. This case highlights the potential for CMV reactivation in patients undergoing ICI therapy, even without prior immunosuppression or irAEs. Notably, the concurrent use of T-VEC raises questions about the interplay between oncolytic viruses, ICIs, and immune modulation. Although T-VEC is not known to directly cause CMV reactivation, its role in amplifying immune responses warrants further investigation. As ICIs and oncolytic viruses become increasingly integral in oncology, clinicians must remain vigilant for rare infectious complications like CMV reactivation. Further research is needed to elucidate mechanisms, identify risk factors, and optimize management strategies for these events.

摘要

巨细胞病毒(CMV)再激活是接受免疫检查点抑制剂(ICI)治疗的患者中一种罕见的并发症,通常发生在针对免疫相关不良事件(irAE)进行免疫抑制治疗之后。在此,我们报告一例独特的严重CMV胃炎病例,该患者接受抗PD-1抗体西米普利单抗和溶瘤病毒talimogene laherparepvec(T-VEC)治疗,之前未发生irAE或接受免疫抑制治疗。一名63岁晚期皮肤鳞状细胞癌男性患者接受西米普利单抗治疗一年,并因疾病复发接受单次T-VEC注射。他出现进行性消化不良、体重显著减轻和营养不良,需要全胃肠外营养。内镜检查发现广泛的胃溃疡,活检证实为CMV胃炎。静脉注射更昔洛韦初始治疗改善了他的病毒载量,但症状缓解甚微。治疗六周后,活检显示CMV感染消退,患者在恢复癌症治疗的同时转为口服缬更昔洛韦进行预防。该病例突出了接受ICI治疗的患者即使没有先前的免疫抑制或irAE也有CMV再激活的可能性。值得注意的是,T-VEC的同时使用引发了关于溶瘤病毒、ICI和免疫调节之间相互作用的问题。虽然已知T-VEC不会直接导致CMV再激活,但其在放大免疫反应中的作用值得进一步研究。随着ICI和溶瘤病毒在肿瘤学中变得越来越不可或缺,临床医生必须对CMV再激活等罕见感染并发症保持警惕。需要进一步研究以阐明机制、识别危险因素并优化这些事件的管理策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/220bf40ef9bd/CCR3-12-e9632-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/ef53aa1742ba/CCR3-12-e9632-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/5d6168e38d21/CCR3-12-e9632-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/9e1df79d65be/CCR3-12-e9632-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/220bf40ef9bd/CCR3-12-e9632-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/ef53aa1742ba/CCR3-12-e9632-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/5d6168e38d21/CCR3-12-e9632-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/9e1df79d65be/CCR3-12-e9632-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f8f/11646813/220bf40ef9bd/CCR3-12-e9632-g004.jpg

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本文引用的文献

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Cemiplimab for the Treatment of Advanced Cutaneous Squamous Cell Carcinoma: Appropriate Patient Selection and Perspectives.西米普利单抗治疗晚期皮肤鳞状细胞癌:合适的患者选择与展望
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Cytomegalovirus Infections in Patients Treated With Immune Checkpoint Inhibitors for Solid Malignancies.接受免疫检查点抑制剂治疗实体恶性肿瘤患者的巨细胞病毒感染
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Isolated Gastritis Secondary to Immune Checkpoint Inhibitors Complicated by Superimposed Cytomegalovirus Infection.免疫检查点抑制剂继发的孤立性胃炎合并巨细胞病毒感染
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