Service de Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, CHU Rennes, Rennes, France.
Département des Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Lyon, France.
Expert Rev Anti Infect Ther. 2022 Sep;20(9):1155-1162. doi: 10.1080/14787210.2022.2101448. Epub 2022 Jul 22.
Chimeric antigen receptor T (CAR-T) cell immunotherapy has revolutionized the prognosis of refractory or relapsed B-cell malignancies. CAR-T cell recipients have immunosuppression generated by B-cell aplasia, leading to a higher susceptibility to respiratory virus infections and poor response to vaccination.
This review focuses on the challenge posed by B-cell targeted immunotherapies: managing long-lasting B-cell impairment during the successive surges of a deadly viral pandemic. We restricted this report to data regarding vaccine efficacy in CAR-T cell recipients, outcomes after developing COVID-19 and specificities of treatment management. We searched in MEDLINE database to identify relevant studies until 31 March 2022.
Among available observational studies, the pooled mortality rate reached 40% in CAR-T cell recipients infected by SARS-CoV-2. Additionally, vaccine responses seem to be widely impaired in recipients (seroconversion 20%, T-cell response 50%). In this setting of B-cell depletion, passive immunotherapy is the backbone of treatment. Convalescent plasma therapy has proven to be a highly effective curative treatment with rare adverse events. Neutralizing monoclonal antibodies could be used as pre-exposure prophylaxis or early treatment but their neutralizing activity is constantly challenged by new variants. In order to reduce viral replication, direct-acting antiviral drugs should be considered.
嵌合抗原受体 T（CAR-T）细胞免疫疗法彻底改变了难治性或复发性 B 细胞恶性肿瘤的预后。CAR-T 细胞受者由于 B 细胞发育不全而产生免疫抑制，导致对呼吸道病毒感染的易感性增加和疫苗接种反应不佳。
本篇综述重点关注针对 B 细胞的免疫疗法带来的挑战：在致命性病毒大流行的连续浪潮中，应对持续存在的 B 细胞损伤。本报告仅限于与 CAR-T 细胞受者疫苗效力、感染 SARS-CoV-2 后的结果以及治疗管理的特异性相关的数据。我们在 MEDLINE 数据库中进行检索，截至 2022 年 3 月 31 日，检索到相关研究。
在现有观察性研究中，CAR-T 细胞受者感染 SARS-CoV-2 的死亡率达到 40%。此外，受者的疫苗反应似乎广泛受损（血清转化率 20%，T 细胞反应 50%）。在这种 B 细胞耗竭的情况下，被动免疫疗法是治疗的基础。恢复期血浆疗法已被证明是一种非常有效的治疗方法，不良反应罕见。中和单克隆抗体可作为暴露前预防或早期治疗使用，但它们的中和活性不断受到新变体的挑战。为了降低病毒复制，应考虑使用直接作用抗病毒药物。
