A phase II randomised controlled trial of adjuvant tumour-infiltrating lymphocytes for pretreatment Epstein-Barr virus DNA-selected high-risk nasopharyngeal carcinoma patients.
A phase II randomised controlled trial of adjuvant tumour-infiltrating lymphocytes for pretreatment Epstein-Barr virus DNA-selected high-risk nasopharyngeal carcinoma patients.
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DOI：
10.1016/j.ejca.2023.112965
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发表时间：
2023-07
影响因子：
8.4
通讯作者：
Yujing Liang;Qiu-Yan Chen;Jing-xiao Xu;Xiu-Feng Liu;J. Xia;Liting Liu;Shanshan Guo;Bin Song;Pan Wang;Ji-Bin Li;Qing Liu;H. Mo;Ling Guo;R. Sun;D. Luo;Jia He;Yi-na Liu;Caiping Nie;L. Tang;Jiang Li;H. Mai
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文献类型：
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作者：
Yujing Liang;Qiu-Yan Chen;Jing-xiao Xu;Xiu-Feng Liu;J. Xia;Liting Liu;Shanshan Guo;Bin Song;Pan Wang;Ji-Bin Li;Qing Liu;H. Mo;Ling Guo;R. Sun;D. Luo;Jia He;Yi-na Liu;Caiping Nie;L. Tang;Jiang Li;H. Mai
目的观察鼻咽癌患者同期放化疗后应用辅助性自体肿瘤浸润性淋巴细胞(TIL)治疗鼻咽癌的安全性和客观性。方法与资料随机将156例III-IVb期≥病毒感染患者随机分为联合TIL输注组(n=78)和单纯CCRT组(n=78)。所有患者均接受CCRT，TIL组患者在CCRT后1周内接受TIL输注。结果经过62.3个月的中位随访期，CCRT加TIL输注组与单纯CCRT组的3年PFS率无显著差异(75.6%比74.4%，危险比1.08；95%可信区间0.62-1.89)。TIL输注是安全的，没有3级或4级不良反应，所有的高度不良反应都与CCRT引起的骨髓抑制有关。探索性分析显示，在循环CD8+TIM3+细胞、血清IL-8或PD-L1水平较低的患者中，TIL可观察到潜在的生存益处。预后良好的患者输注的TIL产品与干扰素-γ和一系列炎症相关基因的转录增加以及较低的耗竭评分有关。结论高危鼻咽癌患者应用CCRT加TIL延长PFS的主要目标未达到。这些发现可能为未来的试验设计提供证据，该试验旨在调查高危鼻咽癌患者中基于CCRT的TILs和免疫检查点抑制剂的组合。试验注册号NCT02421640
PurposeThe safety and objective clinical responses were observed in the phase I study using adjuvant autologous tumour-infiltrating lymphocytes (TILs) following concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients.Methods and materialsOne hundred fifty-six patients with stage III–IVb and pretreatment Epstein–Barr virus DNA levels of ≥4000 copies/ml were randomly assigned to receive CCRT combined with TIL infusion (n= 78) or CCRT alone (n= 78). All patients received CCRT and patients assigned to the TIL group received TIL infusion within 1 week after CCRT. The primary endpoint was investigator-assessed progression-free survival (PFS) at 3 years.ResultsAfter a median follow-up of 62.3 months, no significant difference was observed in the 3-year PFS rate between the CCRT plus TIL infusion group and CCRT alone group (75.6% versus 74.4%, hazard ratios, 1.08; 95% confidence intervals, 0.62–1.89). TIL infusion was safe without grade 3 or 4 adverse events and all the high-grade adverse effects were associated with myelosuppression caused by CCRT. Exploratory analysis showed that a potential survival benefit was observed with TILs in patients with lower levels of circulating CD8+TIM3+ cells, serum IL-8 or PD-L1. The infused TIL products in patients with favourable outcomes were associated with increased transcription of interferon-γ and a series of inflammatory related genes and a lower exhausted score.ConclusionThe primary objective of prolonging PFS with CCRT plus TILs in high-risk NPC patients was not met. These findings may provide evidence for the design of future trials investigating the combination of TILs plus immune checkpoint inhibitors based on CCRT in high-risk NPC patients.Trial registration numberNCT02421640