Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations.
Rare immune-related adverse events in patients with melanoma: incidence, spectrum, and clinical presentations.
复制标题
DOI：
10.1080/2162402x.2023.2188719
复制
发表时间：
2023
期刊：
影响因子：
7.2
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫相关不良事件（irAEs）是免疫检查点抑制剂治疗（ICI）的副作用。虽然常见的免疫相关不良事件（RirAEs）已经有了很好的特征，但由于发病率低，关于罕见免疫相关不良事件（RirAEs）的数据更有限。缺乏这些实体的特征导致了准确诊断和管理的困难。在这里，我们对三家机构（范德比尔特大学医学中心、马萨诸塞州总医院和澳大利亚黑色素瘤研究所）接受ICIs（抗PD-1/L1、抗CTLA-4和联合阻断PD-1/CTLA-4）治疗后发生RirAEs的所有III/IV期黑色素瘤患者进行了多机构分析。RirAEs被定义为在大约<1%的抗pd -1治疗患者或<2%的联合治疗患者中发生的RirAEs。在接受ICIs的2834例患者中，82例发生了RirAEs，并且PD-1/CTLA-4阻断剂联合使用（4.6%）比抗PD-1/L1药物联合使用（2.8%）更为常见。从ICI开始到RirAE的总中位时间为86天（四分位数范围42-235天），联合治疗的发病时间明显提前（p < 0.001）。RirAEs的谱跨越了几个器官系统。大多数rirae为2级（57例[41.3%]）和3级（40例[29.0%]），4级（11例[8.0%]）和5级（5例[3.6%]）事件相对较少。通常需要类固醇再升级（21.4%）或额外的免疫抑制（13.8%）。复发率为22.6%；37.1%有新的irae，并有再挑战。总之，总的来说，在接受抗pd -1治疗的黑色素瘤患者中，2-5%的患者出现了与ICIs相关的RirAEs。经常需要使用类固醇再升级和替代免疫抑制，但致命的irae相当罕见。
Immune-related adverse events (irAEs) are side effects of immune checkpoint inhibitor therapy (ICI). While common irAEs have been well characterized, there are more limited data on rare immune related adverse events (RirAEs) due to low incidence. Lack of characterization of these entities has led to difficulties in accurate diagnosis and management. Here, we conducted a multi-institution analysis of all patients with stage III/IV melanoma who developed RirAEs after being treated with ICIs (anti-PD-1/L1, anti-CTLA-4, and combination PD-1/CTLA-4 blockade) at three institutions (Vanderbilt University Medical Center, Massachusetts General Hospital, and Melanoma Institute of Australia). RirAEs were defined as those occurring in approximately <1% of patients treated with anti-PD-1 or <2% with combination. Of 2834 patients who received ICIs, 82 developed RirAEs and were more common with combination PD-1/CTLA-4 blockade (4.6%) vs. anti-PD-1/L1 agents (2.8%). Overall median time from ICI start to RirAE was 86 days (interquartile range 42–235 days) with significantly earlier onset in combination therapy (p < 0.001). The spectrum of RirAEs spanned across several organ systems. Most RirAEs were grade 2 (57 [41.3%]) and grade 3 (40 [29.0%]) with relatively few grade 4 (11 [8.0%]) or 5 (5 [3.6%]) events. Steroid re-escalation (21.4%) or additional immunosuppression (13.8%) were commonly required. RirAE recurrence occurred in 22.6% with ICI rechallenge; 37.1% had new irAEs with rechallenge. In conclusion, RirAEs associated with ICIs in melanoma patients occurred, in aggregate, in 2–5% of patients treated with anti-PD-1-based therapy. Steroid re-escalation and alternative immunosuppression use were frequently required but fatal irAEs were fairly uncommon.