Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St Petersburg, Florida, USA
Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Immunother Cancer. 2023 Jan;11(1). doi: 10.1136/jitc-2022-005957.
BACKGROUND: Immunocompromised patients are at increased risk of SARS-CoV-2 infections. Patients undergoing chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory B-cell malignancies are uniquely immunosuppressed due to CAR T-mediated B-cell aplasia (BCA). While SARS-CoV-2 mortality rates of 33%-40% are reported in adult CAR T-cell recipients, outcomes in pediatric and young adult CAR T-cell recipients are limited. METHODS: We created an international retrospective registry of CAR T recipients aged 0-30 years infected with SARS-CoV-2 within 2 months prior to or any time after CAR T infusion. SARS-CoV-2-associated illness was graded as asymptomatic, mild, moderate, or severe COVID-19, or multisystem inflammatory syndrome in children (MIS-C). To assess for risk factors associated with significant SARS-CoV-2 infections (infections requiring hospital admission for respiratory distress or supplemental oxygen), univariate and multivariable regression analyses were performed. RESULTS: Nine centers contributed 78 infections in 75 patients. Of 70 SARS-CoV-2 infections occurring after CAR T infusion, 13 (18.6%) were classified as asymptomatic, 37 (52.9%) mild, 11 (15.7%) moderate, and 6 (8.6%) severe COVID-19. Three (4.3%) were classified as MIS-C. BCA was not significantly associated with infection severity. Prior to the emergence of the Omicron variant, of 47 infections, 19 (40.4%) resulted in hospital admission and 7 (14.9%) required intensive care, while after the emergence of the Omicron variant, of 23 infections, only 1 (4.3%) required admission and the remaining 22 (95.7%) had asymptomatic or mild COVID-19. Death occurred in 3 of 70 (4.3%); each death involved coinfection or life-threatening condition. In a multivariable model, factors associated with significant SARS-CoV-2 infection included having two or more comorbidities (OR 7.73, CI 1.05 to 74.8, p=0.048) and age ≥18 years (OR 9.51, CI 1.90 to 82.2, p=0.014). In the eight patients infected with SARS-CoV-2 before CAR T, half of these patients had their CAR T infusion delayed by 15-30 days. CONCLUSIONS: In a large international cohort of pediatric and young adult CAR-T recipients, SARS-CoV-2 infections resulted in frequent hospital and intensive care unit admissions and were associated with mortality in 4.3%. Patients with two or more comorbidities or aged ≥18 years were more likely to experience significant illness. Suspected Omicron infections were associated with milder disease.
背景:免疫功能低下的患者感染 SARS-CoV-2 的风险增加。由于嵌合抗原受体 (CAR) T 细胞介导的 B 细胞耗竭 (BCA),接受复发/难治性 B 细胞恶性肿瘤 CAR-T 细胞治疗的患者具有独特的免疫抑制作用。尽管成人 CAR-T 细胞受者的 SARS-CoV-2 死亡率为 33%-40%,但儿科和年轻成人 CAR-T 细胞受者的结果有限。
方法:我们创建了一个国际回顾性登记处,登记了在 CAR-T 输注前 2 个月内或之后任何时间感染 SARS-CoV-2 的 0-30 岁 CAR-T 受体。将 SARS-CoV-2 相关疾病分为无症状、轻度、中度或重度 COVID-19,或儿童多系统炎症综合征 (MIS-C)。为了评估与严重 SARS-CoV-2 感染(因呼吸窘迫或补充氧气而需要住院治疗的感染)相关的风险因素,进行了单变量和多变量回归分析。
结果:9 个中心共提供了 78 例感染,涉及 75 例患者。在 CAR-T 输注后发生的 70 例 SARS-CoV-2 感染中,13 例(18.6%)为无症状,37 例(52.9%)为轻度,11 例(15.7%)为中度,6 例(8.6%)为严重 COVID-19。3 例(4.3%)为 MIS-C。BCA 与感染严重程度无显著相关性。在 Omicron 变异出现之前,47 例感染中,19 例(40.4%)需要住院治疗,7 例(14.9%)需要重症监护,而在 Omicron 变异出现之后,23 例感染中,仅 1 例(4.3%)需要住院治疗,其余 22 例(95.7%)为无症状或轻度 COVID-19。70 例中有 3 例(4.3%)死亡;每例死亡均涉及合并感染或危及生命的情况。在多变量模型中,与严重 SARS-CoV-2 感染相关的因素包括有两种或两种以上合并症(OR 7.73,CI 1.05 至 74.8,p=0.048)和年龄≥18 岁(OR 9.51,CI 1.90 至 82.2,p=0.014)。在 8 例在 CAR-T 前感染 SARS-CoV-2 的患者中,这些患者中有一半将 CAR-T 输注延迟了 15-30 天。
结论:在一个大型的国际儿科和年轻成人 CAR-T 受体队列中,SARS-CoV-2 感染导致频繁住院和入住重症监护病房,并导致 4.3%的患者死亡。有两种或两种以上合并症或年龄≥18 岁的患者更有可能出现严重疾病。疑似 Omicron 感染与疾病较轻有关。
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