CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma.
Prognostic significance of PET/CT for CAR T cell therapy in relapsed/refractory multiple myeloma.
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PET/CT 在多发性骨髓瘤 (MM) 分期和检测髓外病变 (EMD) 中发挥重要作用;然而,其在接受已商业化 CAR-T 细胞疗法治疗的患者中的作用尚不清楚。
我们评估了 61 例接受 CAR-T 细胞产品治疗的患者。53 例患者在 CAR-T 输注前有 PET/CT 资料,43 例在第 30 天进行了随访 PET/CT。PET/CT 的检查结果与输注后 (CAR) T 单细胞动力学、适应性和 T 细胞受体多样性,以及肿瘤负荷和炎症的血清学标志物相关。非骨依赖性 EMD 患者的中位无进展生存期更差 (PFS:3 vs. 15 个月,p = 0.01)。单因素和多因素分析显示,与较差 PFS 相关的是 EMD,而非病灶数量或代谢肿瘤体积 (MTV)。高 MTV 与较高的基线 sBCMA 和白细胞介素-6 水平相关,但与 CAR-T 细胞扩增受损或旁观者 T 细胞区室适应性下降无关。随访 PET/CT 识别出达到代谢完全缓解的患者,而代谢完全缓解与更好的 PFS 相关。PET/CT 可识别 CAR-T 细胞治疗后复发高风险的患者。
PET/CT plays an important role in staging of multiple myeloma (MM) and detecting extramedullary disease (EMD); however, its role in patients treated with commercially available CAR T cell therapies is unclear.
We evaluated 61 patients treated with CAR T cell products. In 53 patients, PET/CT was available before CAR T infusion, and 43 had follow-up PET/CT on day 30. Findings from PET/CT were correlated to (CAR) T single-cell dynamics, fitness and T cell receptor diversity after infusion, and serological markers of tumor burden and inflammation. Patients with bone-independent EMD had inferior median progression-free survival (PFS: 3 vs. 15 months, p = 0. 01).
Univariate and multivariate analysis showed that EMD but not the number of lesions or metabolic tumor volume (MTV) were associated with inferior PFS. High MTV was connected to higher baseline sBCMA and Interleukin-6 levels, but not associated with hampered CAR T cell expansion or decreased fitness of the bystander T cell compartment. Follow-up PET/CTs identified patients with metabolic complete remissions, which were associated with better PFS. PET/CT identifies patients with high risk of relapse after CAR T cell therapy.
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