1Department of Dermatology, Caen-Normandie University Hospital, Caen, France; Interdisciplinary Research Unit for Cancer Prevention and Treatment, Université de Caen Normandie Inserm Anticipe UMR 1086, Normandie Univ, Research Building, Caen, Franc.
Department of Plastic Surgery, Nantes University Hospital, Nantes, France.
Acta Oncol. 2024 Nov 7;63:867-877. doi: 10.2340/1651-226X.2024.40495.
In patients with metastatic melanoma who respond to anti-PD-1 therapy, the proliferation of intra-tumour CD8+ T cells is directly correlated with the clinical response, making tumour-infiltrating lymphocytes (TILs) a treatment of interest in combination with a PD-1 inhibitor, which is the undisputed gold standard in the management of metastatic melanoma. The aim of this trial was, therefore, to evaluate the safety and efficacy of sequential combination therapy consisting of nivolumab (a PD-1 inhibitor) and TILs adoptive T cells in patients with metastatic melanoma.
We performed an exploratory, prospective, single-centre, open-label, non-randomised, uncontrolled phase I/II study. We enrolled 10 previously untreated patients with advanced melanoma. The treatment regimen was neoadjuvant anti-PD-1 therapy followed by 2 injections of TILs and a second sequence of anti-PD-1 therapy.
Among the four patients who received the autologous TILs + nivolumab combination, three (75%) achieved an objective response (two achieved a partial response [PR] at the end of the study, two achieved a complete response [CR]), and one achieved a CR at the end of the study. Among these three patients, one had a PR, and two had stable disease (SD) after the nivolumab course and before any TILs administration, reinforcing the importance of the tumour response after TILs injection. These responses were persistent, ranging from 9 months to 3.4 years.
在对抗 PD-1 治疗有反应的转移性黑色素瘤患者中，肿瘤内 CD8+T 细胞的增殖与临床反应直接相关，这使得肿瘤浸润淋巴细胞（TILs）成为与 PD-1 抑制剂联合治疗的一种有吸引力的治疗方法，PD-1 抑制剂是转移性黑色素瘤治疗的金标准。因此，本试验旨在评估nivolumab（一种 PD-1 抑制剂）和 TILs 过继性 T 细胞序贯联合治疗在转移性黑色素瘤患者中的安全性和疗效。
我们进行了一项探索性、前瞻性、单中心、开放标签、非随机、非对照的 I/II 期研究。我们招募了 10 名未经治疗的晚期黑色素瘤患者。治疗方案为新辅助抗 PD-1 治疗，随后进行 2 次 TILs 注射和第二次抗 PD-1 治疗。
在接受自体 TILs+nivolumab 联合治疗的 4 名患者中，有 3 名（75%）获得了客观缓解（2 名在研究结束时达到部分缓解[PR]，2 名达到完全缓解[CR]），1 名在研究结束时达到 CR。在这 3 名患者中，1 名有 PR，2 名在接受 nivolumab 治疗后和任何 TILs 治疗前有 SD，这强调了 TILs 注射后肿瘤反应的重要性。这些反应是持续的，从 9 个月到 3.4 年不等。
