Pozas Javier, Cheruvu Sowmya, Jaganathan Poorni Priya, Ganesan Priya, Modi Arjun, Larkin James, Cossar Laura, Olsson-Brown Anna, Johnson Alexandra, Garbutt Nicholas, Lee Rebecca, Jones James, Macklin-Doherty Aislinn, Young Kate
Department of Medical Oncology, The Royal Marsden Hospital NHS Foundation Trust, London SW3 6JJ, UK.
Department of Medical Oncology, University College London Hospitals NHS Trust, London NW1 2PB, UK.
Cancers (Basel). 2025 Jul 25;17(15):2461. doi: 10.3390/cancers17152461.
BACKGROUND/OBJECTIVES: Immune checkpoint inhibitors have significantly transformed the treatment paradigm of advanced melanoma, leading to substantial improvements in survival outcomes. However, this therapeutic success is accompanied by a spectrum of treatment-related adverse events, some of which are increasingly recognised as enduring and non-reversible. Whilst early-onset immune-related toxicities have been well characterized, late-onset toxicities, often emerging in patients with long-term disease control, remain understudied and are frequently overlooked.
To address this knowledge gap, we conducted a retrospective multicentre study in three UK tertiary referral centres, exploring immune-related adverse events in 246 patients with melanoma who received immune checkpoint inhibitors in the advanced setting. We defined late-onset immune-related adverse events as those occurring at least 3 months after the last cycle of immune checkpoint inhibitors.
Although most patients experienced early-onset toxicity, almost 15% of patients developed late-onset immune-related adverse events, including skin rash, colitis, hepatitis, and arthritis, among others. These were often challenging to manage and necessitated the use of systemic steroids. Up to 2% of patients presented ultra-late-onset toxicities, defined as those events occurring at least 12 months after treatment completion.
This study provides valuable insights into the characteristics of late-onset immune-related adverse events. To further advance our understanding of these late-onset toxicities, dedicated prospective studies are needed to assess risk factors associated with their development and their impact on quality of life. Additionally, translational research focused on finding predictive biomarkers is essential to identify patients at a higher risk of developing delayed adverse events and to understand how best to manage them.
背景/目的：免疫检查点抑制剂显著改变了晚期黑色素瘤的治疗模式，使生存结果有了实质性改善。然而，这种治疗成功伴随着一系列与治疗相关的不良事件，其中一些越来越被认为是持久且不可逆的。虽然早发性免疫相关毒性已得到充分表征，但晚发性毒性，通常出现在疾病长期得到控制的患者中，仍未得到充分研究且经常被忽视。
为填补这一知识空白，我们在英国的三个三级转诊中心进行了一项回顾性多中心研究，探讨246例在晚期接受免疫检查点抑制剂治疗的黑色素瘤患者的免疫相关不良事件。我们将晚发性免疫相关不良事件定义为在最后一个免疫检查点抑制剂治疗周期后至少3个月发生的事件。
尽管大多数患者经历了早发性毒性，但近15%的患者出现了晚发性免疫相关不良事件，包括皮疹、结肠炎、肝炎和关节炎等。这些不良事件往往难以处理，需要使用全身性类固醇。高达2%的患者出现超晚发性毒性，定义为在治疗完成后至少12个月发生的事件。
本研究为晚发性免疫相关不良事件的特征提供了有价值的见解。为了进一步加深我们对这些晚发性毒性的理解，需要开展专门的前瞻性研究来评估与其发生相关的风险因素及其对生活质量的影响。此外，专注于寻找预测生物标志物的转化研究对于识别发生延迟不良事件风险较高的患者以及了解如何最好地管理这些事件至关重要。
