Abstract:
Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation. Other immunotherapy strategies, such as oncolytic virotherapy for injectable cutaneous melanoma and bispecific T-cell engager therapy for HLA-A*02:01 genotype-positive uveal melanoma, are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous melanoma, traditional immunotherapy biomarkers (ie, programmed death-ligand 1 expression, tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using immunotherapy to treat melanoma, with topics including therapy selection in the advanced and perioperative settings, intratumoral immunotherapy, when to use immunotherapy for patients with BRAFV600-mutated disease, management of patients with brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.
摘要:
自从十多年前首次批准用于治疗皮肤黑色素瘤的免疫检查点抑制剂(ICIs)以来,免疫疗法完全改变了这种化疗耐药疾病的治疗前景。包括针对程序性细胞死亡蛋白1(PD-1)的ICI与抗细胞毒性T淋巴细胞抗原-4(CTLA-4)药物的联合治疗方案,或,最近,抗淋巴细胞激活基因3(LAG-3)剂,已经获得了治疗转移性皮肤黑色素瘤的监管批准,长期随访数据表明某些晚期疾病患者有治愈的可能性。在可切除设置中,辅助ICIs延长无复发生存期,新辅助治疗策略是一个活跃的研究领域。其他免疫治疗策略,例如可注射皮肤黑色素瘤的溶瘤病毒疗法和HLA-A*02:01基因型阳性葡萄膜黑色素瘤的双特异性T细胞接合剂疗法,也可用于患者。尽管这些方案对许多皮肤黑色素瘤患者有显著疗效,传统的免疫疗法生物标志物(即,程序性死亡-配体1表达,肿瘤突变负担,T细胞浸润和/或微卫星稳定性)无法可靠地预测反应。此外,ICI与独特的毒性特征有关,特别是抗PD-1+抗CTLA-4药物的高活性组合。癌症免疫治疗协会(SITC)召集了一个专家小组,以制定有关治疗黑色素瘤的免疫治疗的临床实践指南,包括罕见的疾病亚型(例如,葡萄膜,粘膜),目的是通过向肿瘤社区提供指导来改善患者护理。根据已发表的数据和临床经验,专家小组为使用免疫疗法治疗黑色素瘤的医疗保健专业人员制定了基于证据和共识的建议,主题包括高级和围手术期的治疗选择,肿瘤内免疫治疗,何时使用免疫疗法治疗BRAFV600突变的疾病,脑转移患者的管理,治疗反应评估,特殊患者群体,患者教育,生活质量,和生存,在其他人中。