Department of Medicine, University of Washington, Seattle, WA.
Vaccine and Infectious Disease Division.
Blood. 2020 Aug 20;136(8):925-935. doi: 10.1182/blood.2019004000.
Adoptive immunotherapy using B-cell-targeted chimeric antigen receptor (CAR)-modified T cells to treat hematologic malignancies is transforming cancer care for patients with refractory or relapsed diseases. Recent and anticipated regulatory approval for products targeting acute lymphoblastic leukemia, lymphomas, and multiple myeloma have led to global implementation of these novel treatments. The rapidity of commercial utilization of CAR-T-cell therapy has created a largely unexplored gap in patient supportive-care approaches. Such approaches are critical in these complex patients given their high net state of immunosuppression prior to CAR-T-cell infusion coupled with unique acute and persistent insults to their immune function after CAR-T-cell infusion. In this "How I Treat" article, we focus on key questions that arise during 3 phases of management for patients receiving CD19-targeted CAR-T cells: pre CAR-T-cell infusion, immediate post CAR-T-cell infusion, and long-term follow-up. A longitudinal patient case is presented for each phase to highlight fundamental issues including infectious diseases screening, antimicrobial prophylaxis, immunoglobulin supplementation, risk factors for infection, and vaccination. We hope this discussion will provide a framework for institutions and health care providers to formulate their own approach to preventing infections in light of the paucity of data specific to this treatment modality.
采用针对 B 细胞的嵌合抗原受体(CAR)修饰的 T 细胞进行过继免疫治疗以治疗血液系统恶性肿瘤,正在改变难治性或复发性疾病患者的癌症治疗模式。针对急性淋巴细胞白血病、淋巴瘤和多发性骨髓瘤的产品的最新和预期的监管批准,导致这些新疗法在全球范围内得到应用。CAR-T 细胞疗法的商业应用速度之快,在患者支持性护理方法方面造成了一个很大程度上尚未探索的空白。鉴于这些复杂患者在接受 CAR-T 细胞输注前处于高度免疫抑制的净状态,并且在接受 CAR-T 细胞输注后其免疫功能会出现独特的急性和持续性损伤,因此此类方法对于这些患者至关重要。在这篇“我如何治疗”文章中,我们重点讨论了接受 CD19 靶向 CAR-T 细胞治疗的患者在 3 个管理阶段出现的关键问题:CAR-T 细胞输注前、CAR-T 细胞输注后即刻和长期随访。针对每个阶段都呈现了一个纵向的患者病例,以突出说明包括传染病筛查、抗菌预防、免疫球蛋白补充、感染风险因素和疫苗接种等基本问题。我们希望,鉴于针对这种治疗方式的数据稀缺,本讨论将为医疗机构和医疗保健提供者提供一个制定预防感染方案的框架。