决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Viral Reactivation in Multiple Myeloma Patients Receiving Anti-BCMA Chimeric Antigen Receptor T-Cell Therapy.
这些发现表明,尽管CMV和EBV再激活在抗BCMA CAR-T后相对常见,但它们很少与有意义的疾病相关,且其风险不超过CD19靶向治疗的风险。
CAR-T(CAR-T)细胞疗法已成为许多血液系统恶性肿瘤的标准治疗,并显著改变了治疗结局。然而,CAR-T 疗法与特定的毒性相关,包括感染。尽管 anti-CD19 CAR-T 的风险已得到充分描述,但多发性骨髓瘤(MM)中 B 细胞成熟抗原(BCMA)靶向 CAR-T 后的感染性并发症仍研究不足。在本研究中,我们评估了 75 例接受 anti-BCMA CAR-T 治疗 MM 的患者中巨细胞病毒(CMV)、EB 病毒(EBV)和腺病毒(ADV)再激活的发生率及临床影响,并将其与 60 例接受商业化 anti-CD19 CAR-T 治疗 B 细胞淋巴瘤(BCL)的患者进行比较。MM 组中 CMV 和 EBV 的病毒再激活率分别为 20% 和 8%,而 BCL 组分别为 31.7% 和 3%。两个队列中均未观察到 ADV 再激活。大多数 CMV 再激活(MM 队列中 87%,BCL 队列中 68.5%)为无症状且临床上无显著意义,并且对无进展生存期(PFS)或总死亡率没有影响。总体而言,这些发现表明,尽管 anti-BCMA CAR-T 后 CMV 和 EBV 再激活相对常见,但它们很少与有临床意义的疾病相关,且风险不超过 CD19 靶向治疗。因此,在无症状患者中,对这些病毒进行常规抢先筛查可能并无必要。
Chimeric antigen receptor T (CAR-T) cell therapy has become a standard of care for many hematological malignancies, and has significantly transformed treatment outcomes. However, CAR-T therapy is associated with specific toxicities, including infections. Although the anti-CD19 CAR-T risks are well-characterized, infectious complications following B-cell maturation antigen (BCMA)-directed CAR-T in multiple myeloma (MM) remain under-researched. In this study, we evaluated the incidence and clinical impact of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus (ADV) reactivations in 75 patients receiving anti-BCMA CAR-T for MM, and compared them to 60 patients receiving commercial anti-CD19 CAR-T for B-cell lymphoma (BCL). The viral reactivation rates were 20% for CMV and 8% for EBV in the MM group, vs. 31.7% and 3%, respectively, in the BCL group. No ADV reactivations were seen in either cohort. Most of the CMV reactivations (87% in the MM cohort and 68.5% in the BCL cohort) were asymptomatic and clinically insignificant, and had no impact on progression-free survival (PFS) or overall mortality. Overall, these findings suggest that although CMV and EBV reactivations are relatively common after anti-BCMA CAR-T, they are rarely associated with meaningful disease, and the risks do not exceed those of CD19-directed therapy. Thus, routine pre-emptive screening for these viruses may be unwarranted in asymptomatic patients.
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