Bishop Michael R
The David and Etta Jonas Center for Cellular Therapy, Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL.
Hematology Am Soc Hematol Educ Program. 2024 Dec 6;2024(1):109-115. doi: 10.1182/hematology.2024000534.
The success of chimeric antigen receptor (CAR) T-cell therapy in adult patients with hematologic malignancies has resulted in a large number of long-term survivors who may experience late complications distinct from those in the early CAR T-cell treatment period. These late complications, defined as occurring more than 90 days after CAR T-cell infusion, include cytopenias, infections, secondary malignancies, and delayed neurotoxicities. Late cytopenias may be from prolonged recovery after lymphodepleting (LD) chemotherapy or arise anew, raising concerns for recurrent primary disease or a secondary malignancy. Cytopenias are treated with supportive care, hematopoietic cytokines, and, occasionally, hematopoietic stem cell support. LD chemotherapy profoundly affects B, T, and natural killer cells. CD19 and B-cell maturation antigen are expressed on normal B cells and plasma cells, respectively, and the targeting of these structures by CAR T-cell products can result in prolonged lymphopenias and hypogammaglobulinemia, making infection an ongoing risk. Late infections are predominantly due to respiratory viruses, reactivation of herpes viruses, and Pneumocystis jirovecii. Patients may require ongoing prophylaxis and immunoglobulin replacement therapy. Although responses may be blunted, vaccinations are generally recommended for most adult CAR T-cell patients. Both hematologic and solid secondary malignancies are a known risk of CAR T-cell therapy; retroviruses used to produce CAR T-cell products have resulted in T-cell cancers secondary to insertional oncogenesis. It is essential to monitor for late complications in adult patients receiving CAR T-cells by using a multidisciplinary approach between referring hematologist oncologists and cell therapy centers to improve the outcomes and quality of life for these patients.
嵌合抗原受体（CAR）T细胞疗法在成年血液系统恶性肿瘤患者中取得的成功，造就了大量长期存活者，他们可能会经历一些与CAR T细胞治疗早期不同的晚期并发症。这些晚期并发症被定义为在CAR T细胞输注90天之后出现，包括血细胞减少、感染、继发性恶性肿瘤和迟发性神经毒性。晚期血细胞减少可能源于淋巴细胞清除（LD）化疗后的恢复时间延长，或者是重新出现，这引发了对原发性疾病复发或继发性恶性肿瘤的担忧。血细胞减少症采用支持性治疗、造血细胞因子进行治疗，偶尔也会采用造血干细胞支持治疗。LD化疗会对B细胞、T细胞和自然杀伤细胞产生深远影响。CD19和B细胞成熟抗原分别在正常B细胞和浆细胞上表达，CAR T细胞产品对这些结构的靶向作用可导致长期淋巴细胞减少和低丙种球蛋白血症，使感染成为持续存在的风险。晚期感染主要由呼吸道病毒、疱疹病毒再激活以及耶氏肺孢子菌引起。患者可能需要持续的预防措施和免疫球蛋白替代疗法。尽管免疫反应可能会减弱，但一般建议大多数成年CAR T细胞患者进行疫苗接种。血液系统和实体继发性恶性肿瘤都是CAR T细胞疗法已知的风险；用于生产CAR T细胞产品的逆转录病毒已导致因插入性致癌作用继发的T细胞癌症。通过转诊血液肿瘤学家和细胞治疗中心之间采用多学科方法，对接受CAR T细胞治疗的成年患者监测晚期并发症至关重要，以改善这些患者的治疗效果和生活质量。
