Felicia Cao, Yueling Xiu, Michael Mohnasky, Jonathan S Serody, Paul Armistead, Gianpietro Dotti, Melody Smith, Jonathan Huggins, Julia Messina, Bhanu Ramachandran, Jennifer Saullo, Joseph Stromberg, Manish K Saha, Megan Walsh, Barbara Savoldo, Natalie Grover, Heather I Henderson, Tessa M. Andermann
{"title":"成人 CD30 嵌合抗原受体 T 细胞疗法后的感染并发症","authors":"Felicia Cao, Yueling Xiu, Michael Mohnasky, Jonathan S Serody, Paul Armistead, Gianpietro Dotti, Melody Smith, Jonathan Huggins, Julia Messina, Bhanu Ramachandran, Jennifer Saullo, Joseph Stromberg, Manish K Saha, Megan Walsh, Barbara Savoldo, Natalie Grover, Heather I Henderson, Tessa M. Andermann","doi":"10.1101/2024.07.10.24310235","DOIUrl":null,"url":null,"abstract":"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. 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引用次数: 0
摘要
越来越多的人认识到,感染是嵌合抗原受体(CAR)T细胞疗法的常见并发症。CD19.CAR T细胞治疗复发/难治性淋巴瘤后的第一年,临床定义的感染发生率为60%-90%,是非复发死亡的最常见原因。然而,针对其他恶性肿瘤的 CAR T 细胞疗法后的感染风险还不十分清楚。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 只在活化的 T 细胞和 B 细胞的一个子集上表达,我们假设与 CD19.CAR T 细胞患者相比,CD30.CAR T 细胞患者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 2016-2021 年间在一家机构接受 CD30.CAR T 细胞治疗的所有 64 例患者,评估了细胞输注后一年内的感染情况,并将这些数据与 2018-2021 年间在同一机构接受 CD19.CAR T 细胞治疗的 50 例患者的当代队列进行了比较。23名CD30.CAR T细胞患者(36%)和18名CD19.CAR T细胞患者(36%)发生了经微生物证实的感染。与CD30.CAR T细胞受者相比,CD19.CAR T细胞组的感染严重程度和细菌感染更高,CD30.CAR T细胞受者更常见的是1级呼吸道病毒感染。我们的数据反映了 CD19.CAR T 细胞患者的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。虽然我们的研究结果需要在更大的群体中进行复制,但它们对CD30.CAR T细胞治疗后的抗菌预防指南具有一定的指导意义。
Infectious Complications Following CD30 Chimeric Antigen Receptor T-Cell Therapy in Adults
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.