不变自然杀伤T细胞输注联合经动脉栓塞与单纯经动脉栓塞治疗肝细胞癌患者的疗效：一项2期随机临床试验
Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.
作者信息
Guo Jia, Bao Xuli, Liu Fuquan, Guo Jiang, Wu Yifan, Xiong Fang, Lu Jun
机构信息
Hepatology and Cancer Biotherapy Ward, Beijing YouAn Hospital, Capital Medical University, Beijing, People's Republic of China.
Department of Interventional Therapy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China.
出版信息
J Hepatocell Carcinoma. 2023 Aug 21;10:1379-1388. doi: 10.2147/JHC.S416933. eCollection 2023.
PURPOSE
Invariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure.
PATIENTS AND METHODS
This open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE-iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety.
RESULTS
Fifty-four patients completed the study. Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3-7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3-3.2 months]; hazard ratio 0.32 [95% CI, 0.16-0.63]; <0.001). Higher ORR and DCR were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE-iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0-13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9-3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95×10/L, P = 0.007) and 12 (1.49 vs 0.89×10/L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1-2.
CONCLUSION
iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.
目的
不变自然杀伤T细胞（iNKT）是具有抗肿瘤免疫能力的CD1d限制性T细胞。自体iNKT细胞治疗肝细胞癌（HCC）的安全性已得到验证。本研究旨在探讨其在经动脉化疗栓塞术（TACE）失败后的晚期HCC中的疗效。
患者与方法
本开放标签、随机、对照试验在三个中心纳入了60例TACE失败后无法切除的HCC患者。采用经动脉栓塞术（TAE）代替TACE以保护iNKT细胞功能。患者被随机分配（1:1）接受每两周一次iNKT细胞输注的TAE治疗（TAE-iNKT）或不接受iNKT细胞输注的TAE治疗。主要终点是无进展生存期（PFS）。次要终点包括总生存期（OS）、客观缓解率（ORR）、疾病控制率（DCR）、生活质量（QoL）、外周血细胞计数和安全性。
结果
54例患者完成了研究。TAE-iNKT组患者的中位PFS显著高于TAE组（5.7个月[95%CI，4.3 - 7.0个月]），TAE组为2.7个月[95%CI，2.3 - 3.2个月]；风险比为0.32[95%CI，0.16 - 0.63]；P<0.001）。与TAE组患者（分别为11%和33%）相比，TAE-iNKT组患者的ORR和DCR更高（分别为52%和85%）。5例TAE-iNKT患者和1例TAE患者达到完全缓解。与TAE组患者（3.0个月[95%CI，2.9 - 3.0个月]）相比，TAE-iNKT组患者QoL恶化的中位时间更长（9.2个月[95%CI，6.0 - 13.3个月]）。在第8周（1.48对0.95×10⁹/L，P = 0.007）和第12周（1.49对0.89×10⁹/L，P = 0.001）时，TAE-iNKT组的平均淋巴细胞数高于TAE组。1例TAE-iNKT患者（4%）和5例TAE患者（19%）发生3级不良事件。所有其他不良事件均为1 - 2级。
结论
在HCC患者的TAE治疗期间，输注iNKT细胞可显著改善PFS、ORR、DCR和QoL，且毒性可控。试验注册ClinicalTrials.gov标识符：NCT04011033。
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