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成人CD30嵌合抗原受体T细胞疗法后的感染性并发症

Infectious Complications Following CD30 Chimeric Antigen Receptor T-Cell Therapy in Adults.

作者信息

Cao Felicia, Xiu Yueling, Mohnasky Michael, Serody Jonathan S, Armistead Paul, Dotti Gianpietro, Smith Melody, Huggins Jonathan, Messina Julia, Ramachandran Bhanu, Saullo Jennifer, Stromberg Joseph, Saha Manish K, Walsh Megan, Savoldo Barbara, Grover Natalie, Henderson Heather I, Andermann Tessa M

出版信息

medRxiv. 2024 Jul 11:2024.07.10.24310235. doi: 10.1101/2024.07.10.24310235.

Abstract

UNLABELLED

Infections are increasingly recognized as a common complication of chimeric antigen receptor (CAR) T-cell therapy. The incidence of clinically-defined infection after CD19.CAR T-cell therapy for relapsed/refractory lymphoma ranges from 60-90% in the first year after CAR T-cell therapy and is the most common cause for non-relapse mortality. However, infectious risk after CAR T-cell therapy targeting other malignancies is not well understood. Herein, we report for the first time, infectious complications after CD30.CAR T-cell treatment for patients with Hodgkin's lymphoma and peripheral T-cell lymphoma. Since CD30 is only expressed on a subset of activated T and B-cells, we hypothesized that CD30.CAR T-cell patients would have reduced incidence and severity of infections after infusion compared to CD19.CAR T-cell patients. We retrospectively evaluated all 64 patients who received CD30.CAR T-cells at a single institution between 2016-2021, and assessed infections within one year after cell infusion, comparing these data to a contemporary cohort of 50 patients who received CD19.CAR T-cells at the same institution between 2018-2021. 23 CD30.CAR T-cell patients (36%) and 18 CD19.CAR T-cell patients (36%) developed a microbiologically confirmed infection. Infection severity and bacterial infections were higher in the CD19.CAR T-cell group compared to CD30.CAR T-cell recipients who more commonly had grade 1 respiratory viral infections. Our data reflect expected outcomes for severity and infection type in CD19.CAR T-cell patients and provide a benchmark for comparison with the novel CD30.CAR T-cell product. Although our findings require replication in a larger cohort, they have implications for antimicrobial prophylaxis guidelines after CD30.CAR T-cell therapy.

KEY POINTS

  1. The incidence of infections within the first year after CD30.CAR T-cell therapy was equivalent to that following CD19.CAR T-cell therapy2) Viral infections were more common after CD30.CAR T-cell therapy but bacterial infections predominated after CD19.CAR T-cell therapy.
摘要

未标记

感染日益被认为是嵌合抗原受体(CAR)T细胞疗法的常见并发症。在复发/难治性淋巴瘤的CD19 CAR T细胞治疗后,临床定义的感染发生率在CAR T细胞治疗后的第一年为60%-90%,是非复发死亡率的最常见原因。然而,针对其他恶性肿瘤的CAR T细胞治疗后的感染风险尚不清楚。在此,我们首次报告了霍奇金淋巴瘤和外周T细胞淋巴瘤患者接受CD30 CAR T细胞治疗后的感染并发症。由于CD30仅在一部分活化的T细胞和B细胞上表达,我们假设与CD19 CAR T细胞患者相比,CD30 CAR T细胞患者在输注后感染的发生率和严重程度会降低。我们回顾性评估了2016年至2021年在单一机构接受CD30 CAR T细胞的所有64例患者,并评估了细胞输注后一年内的感染情况,将这些数据与2018年至2021年在同一机构接受CD19 CAR T细胞的50例当代队列患者的数据进行比较。23例CD30 CAR T细胞患者(36%)和18例CD19 CAR T细胞患者(36%)发生了微生物学确诊的感染。与更常见1级呼吸道病毒感染的CD30 CAR T细胞接受者相比,CD19 CAR T细胞组的感染严重程度和细菌感染更高。我们的数据反映了CD19 CAR T细胞患者感染严重程度和感染类型的预期结果,并为与新型CD30 CAR T细胞产品进行比较提供了基准。尽管我们的发现需要在更大的队列中进行重复验证,但它们对CD30 CAR T细胞治疗后的抗菌预防指南具有启示意义。

关键点

1)CD30 CAR T细胞治疗后第一年内的感染发生率与CD19 CAR T细胞治疗后相当。2)CD30 CAR T细胞治疗后病毒感染更常见,但CD19 CAR T细胞治疗后细菌感染占主导。

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