Extended Follow-Up of Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-Risk Resected Melanoma.
Extended Follow-Up of Chronic Immune-Related Adverse Events Following Adjuvant Anti-PD-1 Therapy for High-Risk Resected Melanoma.
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DOI：
10.1001/jamanetworkopen.2023.27145
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发表时间：
2023-08-01
影响因子：
13.8
通讯作者：
Johnson, Douglas B.
中科院分区：
文献类型：
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作者：
Goodman, Rachel S.;Lawless, Aleigha;Woodford, Rachel;Fa'ak, Faisal;Tipirneni, Asha;Patrinely, J. Randall;Yeoh, Hui Ling;Rapisuwon, Suthee;Haydon, Andrew;Osman, Iman;Mehnert, Janice M.;Long, Georgina V.;Sullivan, Ryan J.;Carlino, Matteo S.;Menzies, Alexander M.;Johnson, Douglas B.
这项队列研究检查了美国和澳大利亚6家机构中晚期和转移性黑色素瘤辅助抗可编程细胞死亡-1的慢性免疫相关不良事件的发生率、特征和长期结局。辅助抗程序性细胞死亡-1（抗PD-1）治疗的慢性免疫相关不良事件（irAE）的发生率和长期结局谱是什么？在这项针对318例接受辅助抗PD-1治疗的晚期和转移性黑色素瘤患者的队列研究中，63. 3%的慢性irAE患者（所有接受辅助PD-1治疗的患者的29. 2%）在长期随访时发生持续性irAE。这些结果表明，慢性irAE很常见，而且通常是持续性的，强调在考虑辅助抗PD-1治疗时，仔细的风险-获益分析和长期监测和管理的重要性。抗可编程细胞死亡-1（抗PD-1）在用作高风险切除黑色素瘤的辅助治疗时可改善无复发生存期。然而，它可能导致免疫相关不良事件（irAE），在接受辅助抗PD-1治疗的高风险黑色素瘤患者中，约40%的患者成为慢性。确定辅助抗PD-1治疗引起的慢性irAE的发生率、特征和长期结局。这项回顾性多中心队列研究分析了2015年至2022年期间接受辅助抗PD-1治疗的晚期和转移性黑色素瘤患者，这些患者来自美国和澳大利亚的6家机构，治疗停止后至少进行了18个月的可评价随访（范围：18.2至70.4个月）。慢性irAE（定义为治疗停止后持续至少3个月）的发生率、谱和最终消退与持续性。使用描述性统计分析分类和连续变量。Kaplan-Meier曲线评估生存率，Wilson评分区间用于计算比例的CI。在318例患者中，190例（59.7%）为男性（中位[IQR]年龄为61 [52.3-72.0]岁），270例（84.9%）为皮肤原发性，237例（74.5%）为IIIB或IIIC期。此外，226例患者（63.7%）在治疗期间发生急性irAE，包括44例（13.8%）3 - 5级irAE。147例患者（46. 2%; 95% CI，0. 41 - 0. 52）发生了治疗停止后持续至少3个月的慢性irAE，其中74例（50. 3%）为2级或以上，6例（4. 1%）为3 - 5级，100例（68. 0%）为症状性。在长期随访（中位数[IQR]，1057 [915-1321]天）中，54例患者（36.7%）出现慢性irAE消退（从抗PD-1治疗开始至消退的中位数[IQR]时间为19.7 [14.4-31.5]个月，从抗PD-1治疗停止至消退的中位数[IQR]时间为11.2 [8.1-20.7]个月）。末次随访时存在持续irAE的患者中（原始队列93例[29.2%]; 95% CI，0.25-0.34）; 55 2级或2级以上者占59.1%;有症状者占44.1%; 24（25.8%）正在使用治疗性全身类固醇其中16例（67%）因垂体炎（8例（50.0%））和肾上腺功能不全（8例（50.0%））而使用替代类固醇，42例（45.2%）使用其他治疗。在54例患者中，最常见的持续性慢性irAE为甲状腺功能减退（38例[70.4%]）、关节炎（18例[33.3%]）、皮炎（9例[16.7%]）和肾上腺功能不全（8例[14.8%]）。此外，54例[17.0%]患者发生持续性内分泌病，48例（15.1%）患者发生非内分泌病，9例（2.8%）患者同时发生两种内分泌病。在接受额外免疫治疗的37例慢性irAE患者中，25例（67.6%）对慢性irAE无影响，而12例（32.4%）慢性毒性发作。20例患者（54.1%）发生了明显的irAE。在这项对318例接受辅助抗PD-1治疗的患者进行的队列研究中，慢性irAE很常见，影响不同的器官系统，并且通常持续存在，需要长期随访，需要类固醇和其他管理。这些发现强调了在考虑辅助治疗时持续毒性作用的可能性，并需要长期监测和管理。
This cohort study examined the incidence, characteristics, and long-term outcomes of chronic immune-related adverse events from adjuvant anti–programmable cell death-1 for advanced and metastatic melanoma at 6 institutions in the US and Australia. What are the incidence and spectrum of long-term outcomes of chronic immune-related adverse events (irAEs) from adjuvant anti–programmable cell death-1 (anti–PD-1) therapy? In this cohort study of 318 patients treated with adjuvant anti–PD-1 therapy for advanced and metastatic melanoma, 63.3% of patients with chronic irAEs (29.2% of all patients with adjuvant PD-1 therapy) experienced persistent irAEs with prolonged follow up. These findings suggest that chronic irAEs are common and often persistent, emphasizing the importance of careful risk-benefit analysis and prolonged monitoring and management when considering adjuvant anti–PD-1 therapy. Anti–programmable cell death-1 (anti–PD-1) improves relapse-free survival when used as adjuvant therapy for high-risk resected melanoma. However, it can lead to immune-related adverse events (irAEs), which become chronic in approximately 40% of patients with high-risk melanoma treated with adjuvant anti–PD-1. To determine the incidence, characteristics, and long-term outcomes of chronic irAEs from adjuvant anti–PD-1 therapy. This retrospective multicenter cohort study analyzed patients treated with adjuvant anti–PD-1 therapy for advanced and metastatic melanoma between 2015 and 2022 from 6 institutions in the US and Australia with at least 18 months of evaluable follow-up after treatment cessation (range, 18.2 to 70.4 months). Incidence, spectrum, and ultimate resolution vs persistence of chronic irAEs (defined as those persisting at least 3 months after therapy cessation). Descriptive statistics were used to analyze categorical and continuous variables. Kaplan-Meier curves assessed survival, and Wilson score intervals were used to calculate CIs for proportions. Among 318 patients, 190 (59.7%) were male (median [IQR] age, 61 [52.3-72.0] years), 270 (84.9%) had a cutaneous primary, and 237 (74.5%) were stage IIIB or IIIC at presentation. Additionally, 226 patients (63.7%) developed acute irAEs arising during treatment, including 44 (13.8%) with grade 3 to 5 irAEs. Chronic irAEs, persisting at least 3 months after therapy cessation, developed in 147 patients (46.2%; 95% CI, 0.41-0.52), of which 74 (50.3%) were grade 2 or more, 6 (4.1%) were grade 3 to 5, and 100 (68.0%) were symptomatic. With long-term follow-up (median [IQR], 1057 [915-1321] days), 54 patients (36.7%) experienced resolution of chronic irAEs (median [IQR] time to resolution of 19.7 [14.4-31.5] months from anti–PD-1 start and 11.2 [8.1-20.7] months from anti–PD-1 cessation). Among patients with persistent irAEs present at last follow-up (93 [29.2%] of original cohort; 95% CI, 0.25-0.34); 55 (59.1%) were grade 2 or more; 41 (44.1%) were symptomatic; 24 (25.8%) were using therapeutic systemic steroids (16 [67%] of whom were on replacement steroids for hypophysitis (8 [50.0%]) and adrenal insufficiency (8 [50.0%]), and 42 (45.2%) were using other management. Among the 54 patients, the most common persistent chronic irAEs were hypothyroid (38 [70.4%]), arthritis (18 [33.3%]), dermatitis (9 [16.7%]), and adrenal insufficiency (8 [14.8%]). Furthermore, 54 [17.0%] patients experienced persistent endocrinopathies, 48 (15.1%) experienced nonendocrinopathies, and 9 (2.8%) experienced both. Of 37 patients with chronic irAEs who received additional immunotherapy, 25 (67.6%) experienced no effect on chronic irAEs whereas 12 (32.4%) experienced a flare in their chronic toxicity. Twenty patients (54.1%) experienced a distinct irAE. In this cohort study of 318 patients who received adjuvant anti–PD-1, chronic irAEs were common, affected diverse organ systems, and often persisted with long-term follow-up requiring steroids and additional management. These findings highlight the likelihood of persistent toxic effects when considering adjuvant therapies and need for long-term monitoring and management.
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DOI：
10.1038/s41571-022-00600-w
发表时间：
2022-04
期刊：
Nature reviews. Clinical oncology
影响因子：
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作者：
Johnson DB;Nebhan CA;Moslehi JJ;Balko JM
通讯作者：
Balko JM
影响因子：
28.4
作者：
Patrinely, J. Randall, Jr.;Johnson, Rebecca;Johnson, Douglas B.
通讯作者：
Johnson, Douglas B.
影响因子：
51.1
作者：
Ascierto, Paolo A.;Del Vecchio, Michele;Weber, Jeffrey
通讯作者：
Weber, Jeffrey
影响因子：
158.5
作者：
Eggermont, Alexander M. M.;Blank, Christian U.;Robert, Caroline
通讯作者：
Robert, Caroline
DOI：
10.1093/oncolo/oyac220
发表时间：
2022-12-09
期刊：
The oncologist
影响因子：
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作者：
通讯作者：
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