Safety of adoptive therapy with tumor-infiltrating lymphocytes and high-dose recombinant interleukin 2 in advanced cutaneous melanoma: a systematic review and meta-analysis.

Its combination with nonmyeloablative but lymphodepleting (NMA-LD) chemotherapy and high-dose interleukin 2 (HD-IL-2) inevitably lead to severe treatment-related adverse events.

其与非骨髓消融但淋巴细胞耗竭(NMA-LD)化疗和高剂量白细胞介素2(HD-IL-2)的联合使用不可避免地导致严重的治疗相关不良事件。

The systematic recording of the observed toxicities, which is the aim of the present meta-analysis, will further enhance the implementation and management of this treatment schema.

本荟萃分析旨在系统记录观察到的毒性，这将进一步提高该治疗方案的实施和管理。

materials_and_methods

A comprehensive search was conducted in PubMed up to 29 February 2024.

截至2024年2月29日，在PubMed进行了全面的搜索。

In this meta-analysiswe focused on studies of treatment-refractory advanced cutaneous melanoma with TILs administered in combination with NMA-LD chemotherapy and HD-IL-2 (≥600 000 IU/kg).

在这项荟萃分析中，我们专注于研究治疗难治性晚期皮肤黑色素瘤，其中肿瘤浸润淋巴细胞（TILs）与NMA-LD化疗和HD-IL-2（≥600 000 IU/kg）联合使用。

Our primary endpoint was severe adverse events (AEs) of grade 3 or higher.

我们的主要终点是3级或更高级别的严重不良事件（AEs）。

The safety data were consistently coded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

安全性数据一致使用不良事件通用术语标准（CTCAE）第5版进行编码。

Findings were synthesized using tables, while pooled estimates for groups of AEs of particular interest were derived from random effects models.

研究结果通过表格进行综合，而特定不良事件组的汇总估计值则来自随机效应模型。

Results

A total of 12 HD-IL-2 studies of 670 patients with available toxicity information were included in this meta-analysis.

本荟萃分析共纳入了12项HD-IL-2研究，涉及670名有可用毒性信息的患者。

Blood toxicities were identified as the most common AEs.

血液毒性被确定为最常见的不良事件（AEs）。

In the frame of the formal meta-analysis, the pooled estimate of the probability of febrile neutropenia was 60% [95% confidence interval(CI) 36% to 83%].

在正式的荟萃分析框架内，发热性中性粒细胞减少症发生的概率汇总估计为60% [95% 置信区间 (CI) 36% 至 83%].

The total pooled estimate for the probability of severe 'immunologic reaction' events, was 4% (95% CI 1% to 6%), while the respective probability for experiencing a severe AE in Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) category 'Infections and infestations' was 8% (95% CI 4% to 11%).

严重'免疫反应'事件发生的总概率汇总估计为4% (95% 置信区间 1% 至 6%)，而相应地，在医学监管活动词典（MedDRA）系统器官类（SOC）类别'感染和寄生虫病'中经历严重不良事件的概率为8% (95% 置信区间 4% 至 11%).

In addition, in total, nine fatal (grade 5) AEs were reported, mostly stated as not attributed to the treatment or attributed to NMA/HD-IL-2.

此外，总共报告了九例致命（5级）不良事件，大多数被指出与治疗无关或归因于NMA/HD-IL-2。

Conclusions

TIL-ACT, a new approved and promising therapy for melanoma patients, presents a distinctive toxicity profile that is currently manageable with supportive care methods, with reported toxicities mainly arising from NMA-LD chemotherapy and HD-IL-2, and a low risk of severe immunologic reaction events.

TIL-ACT，一种新批准的、对黑色素瘤患者有前景的治疗方法，呈现出一种独特的毒性特征，目前可以通过支持性护理方法进行管理，报告的毒性主要来自于NMA-LD化疗和HD-IL-2，且严重免疫反应事件的风险较低。

Continued systematic recording and publication of AEs, even the rare ones, and their relation to treatment components, are essential to move the field forward.

持续系统地记录和发布不良事件（AEs），即使是罕见的，以及它们与治疗组成部分的关系，对于推动该领域的发展至关重要。