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

被引：10

作者：

Guo, Jia ^{[1
]}

Bao, Xuli ^{[1
]}

Liu, Fuquan ^{[2
]}

Guo, Jiang ^{[3
]}

Wu, Yifan ^{[2
]}

Xiong, Fang ^{[1
]}

Lu, Jun ^{[1
,4
]}

机构：

[1] Capital Med Univ, Beijing YouAn Hosp, Hepatol & Canc Biotherapy Ward, Beijing, Peoples R China

[2] Capital Med Univ, Beijing Shijitan Hosp, Dept Intervent Therapy, Beijing, Peoples R China

[3] Capital Med Univ, Beijing Ditan Hosp, Dept Intervent Therapy, Beijing, Peoples R China

[4] Capital Med Univ, Beijing YouAn Hosp, Hepatol & Canc Biotherapy Ward, 8 Xi Tou Tiao, Beijing 10069, Peoples R China

来源：

JOURNAL OF HEPATOCELLULAR CARCINOMA | 2023年 / 10卷

基金：

中国国家自然科学基金;

关键词：

hepatocellular carcinoma; invariant natural killer T cell; transarterial embolization; progression-free survival; LIVER-CANCER; NKT CELLS; CHEMOEMBOLIZATION; SURVEILLANCE; ACTIVATION;

D O I：

10.2147/JHC.S416933

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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]; P<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 0.95x10(9)/L, P = 0.007) and 12 (1.49 vs 0.89x10(9)/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.

引用

页码：1379 / 1388

页数：10