背景:免疫检查点抑制剂(ICIs)已经促进了恶性黑色素瘤患者的治疗前景。然而,它们可引起永久性和不可逆的皮肤病免疫相关不良事件(irAEs),可能导致ICI治疗中断或危及生命.评估晚期黑色素瘤的ICIs中严重皮肤科irAE(3级或更高)的风险,我们进行了网络荟萃分析(NMA).
方法:从各种数据库中检索涉及ICIs的II/III期随机对照临床试验(RCT),包括PubMed,Embase,科克伦图书馆,和WebofScience。这些试验从数据库开始到2022年10月15日发表。此外,我们通过NMA评估并比较了与ICI类型和剂量相关的严重皮肤科IRAE的风险.
结果:本研究包括20个II/III期RCTs,共10575名患者。结果表明,与化学疗法相比,ICI具有更高的严重皮肤病的风险。此外,与ICI单药治疗相比,Nivolumab+Ipilimumab联合治疗的风险更高.相对而言,包括Relatlimab+Nivolumab双重ICI治疗的最新治疗选择显示出更低的毒性风险,但高于单独的伊匹单抗。最后,Nivolumab,以每2周3mg/kg的剂量,在晚期黑素瘤患者中,观察到严重皮肤科irAE的最低风险给药方案。
结论:研究结果表明,Nivolumab(1mg/kg)+Ipilimumab(3mg/kg)每3周给药一次,应谨慎用于皮肤科irAE高风险的晚期黑色素瘤患者。虽然我们推荐Nivolumab的首选方案(剂量=3mg/kg,每2周)。
BACKGROUND: Immune checkpoint inhibitors (ICIs) have advanced the therapeutic landscape for malignant melanoma patients. However, they can cause permanent and irreversible dermatologic immune-related adverse events (irAEs) that may lead to interruption of ICI treatment or become life-threatening. To assess the risk of severe dermatologic irAEs (grade 3 or higher) among ICIs for advanced melanoma, we conducted a network meta-analysis (NMA).
METHODS: Phase II/III randomized controlled clinical trials (RCTs) involving ICIs were retrieved from various databases, including PubMed, Embase, Cochrane Library, and Web of Science. These trials were published from the inception of databases to October 15, 2022. In addition, the risk of severe dermatologic irAEs associated with ICI types and doses was evaluated and compared by NMA.
RESULTS: This study included 20 Phase II/III RCTs with a total of 10 575 patients. The results indicated that ICIs carry a higher risk of severe dermatologic irAEs compared to chemotherapy. Additionally, the combinational therapy of Nivolumab + Ipilimumab was associated with a higher risk than ICI monotherapy. Comparatively, the latest treatment option involving dual ICI therapy with Relatlimab + Nivolumab showed a lower toxicity risk, but higher than Ipilimumab alone. Lastly, Nivolumab, at a dose of 3 mg/kg every 2 weeks, was observed as the lowest-risk dosing regimen for severe dermatologic irAEs in patients with advanced melanoma.
CONCLUSIONS: The findings suggest that Nivolumab (1 mg/kg) + Ipilimumab (3 mg/kg) administered every 3 weeks should be used cautiously in patients with advanced melanoma at high risk for dermatologic irAEs. While we recommend the preferred regimen of Nivolumab (dose = 3 mg/kg, every 2 weeks).