肿瘤细胞治疗研究
英文原题:Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution.
Immunological consequences of CAR T-cell therapy: an analysis of infectious complications and immune reconstitution.
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嵌合抗原受体(CAR)T 细胞疗法治疗复发/难治性(R/R)B 细胞肿瘤(如弥漫大 B 细胞淋巴瘤[DLBCL]和多发性骨髓瘤[MM])已显示显著疗效。尽管治疗成功,CAR-T 对免疫系统的长期影响和后遗效应仍未得到充分研究。
本研究报告 52 例患者的 1 年随访分析,其中 42 例为 R/R DLBCL、10 例为 R/R MM;患者接受抗 CD19 或靶向 B 细胞成熟抗原的 CAR-T 细胞治疗,研究重点为免疫重建和感染并发症。
结果显示,CAR-T 治疗会导致 B 细胞和 T 细胞显著耗竭。治疗后 CD4⁺ T 细胞和 CD19⁺ B 细胞再生受损。感染在最初 30 天内更常见。短期随访期间,每 100 个风险观察日的感染密度,DLBCL 患者为 1.8,MM 患者为 4.6;CAR-T 输注后早期以细菌感染为主。
此外,长期随访中感染类型转为病毒感染,感染密度下降;DLBCL 患者为每 100 个风险观察日 0.1 次,MM 患者为 0.4 次。严重 CRS 与迟发性感染风险升高相关。这些发现凸显接受 CAR-T 治疗患者密切监测并采取预防措施的重要性,以降低感染风险并促进免疫恢复。
Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in treating relapsed and refractory (R/R) B-cell neoplasms, such as diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Despite its success, the long-term effects and sequelae of CAR T cells on the immune system remain underexplored.
This study presents a 1-year follow-up analysis of 52 patients (42 with R/R DLBCL and 10 with R/R MM) treated with anti-CD19- and B-cell maturation antigen-targeted CAR T cells, focusing on immune reconstitution and infectious complications.
Our findings reveal that CAR T-cell therapy leads to profound depletion of B and T cells. CD4+ T cells and CD19+ B cells exhibited impaired regeneration after treatment. Infections were more frequent during the first 30 days. In the short-term follow-up, density of infections within 100 days at risk was 1. 8 in patients with DLBCL and 4. 6 in patients with MM, with bacterial infections predominating in this early period after CAR T-cell infusion.
In addition, we observed a shift to viral infections in the long-term follow-up, alongside with a decline in infection density to 0. 1 in patients with DLBCL and 0. 4 infections per 100 days at risk in patients with MM, respectively. Severe cytokine release syndrome was associated with a higher risk of late-onset infections.
These findings highlight the importance of close monitoring and prophylactic measures in patients undergoing CAR T-cell therapy to reduce infection risks and enhance immune recovery.
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