免疫检查点抑制剂控制效应机制并致力于恢复黑色素瘤患者下调的 T 细胞。例如程序性死亡 1 抑制剂和淋巴细胞激活基因 3 抑制剂。程序性死亡 1 抑制剂纳武单抗 (nivolumab) 与淋巴细胞激活基因 3 抑制剂 relatlimab-rmbw 的组合已显示出抗肿瘤活性，并改善了不可切除或转移性黑色素瘤患者的无进展生存期。纳武单抗 (nivolumab) 的固定剂量组合relatlimab 免疫疗法被批准用于患有转移性或不可切除黑色素瘤的成人和 12 岁或以上儿童。 relatlimab 和 nivolumab 的分布容积为 6.6 L，半衰期分别为 27 和 26 天。 nivolumab 稳态清除率为 7.6 mL/h，relatlimab 稳态清除率为 5.5 mL/h。性别、年龄、种族和轻度肝/肾损伤对清除率没有临床影响。 nivolumab/relatlimab-rmbw 的安全性和有效性的暴露-反应关系和药效学反应尚未得到充分表征。安全性问题包括严重和致命的免疫介导的不良反应、输注相关反应以及同种异体造血干细胞移植的并发症和胎儿毒性。剂量取决于患者的年龄和体重。溶液输注时间为 30 分钟。在 RELATIVITY-047 试验中，患者接受 nivolumab 或 nivolumab/relatlimab-rmbw 治疗。结果显示，双联疗法优于单药疗法，无进展生存期为 10.1 个月（95% CI，6.4-15.7），而无进展生存期为 4.6 个月（95% CI，3.4-5.6），风险比为 0.75（95% CI，0.62）。 -0.92); P 分别 = 0.006。与单药治疗相比，没有观察到安全性问题，联合治疗组中 18.9% 的患者发生与治疗相关的不良事件，而单用纳武单抗组中发生治疗相关不良事件的比例为 9.7%。与标准护理相比，新机制和无进展生存期的改善凸显了治疗的进步nivolumab/relatlimab-rmbw 在治疗不可切除和转移性黑色素瘤中的应用。版权所有 © 2023 Wolters Kluwer Health, Inc. 保留所有权利。

Immune checkpoint inhibitors control effector mechanisms and work to restore downregulated T-cells in patients with melanoma. Examples of such include programmed death-1 inhibitors and lymphocyte-activating gene 3 inhibitors. The combination of nivolumab, a programmed death-1 inhibitor, and relatlimab-rmbw, a lymphocyte-activating gene 3 inhibitor, has shown antitumor activity and improved progression-free survival in patients with unresectable or metastatic melanoma.The fixed-dose combination of nivolumab and relatlimab immunotherapy is approved for adults and pediatrics 12 years of age or older with metastatic or unresectable melanoma. Volume of distribution is 6.6 L for relatlimab and nivolumab, and half-life is 27 and 26 days, respectively. Clearance at steady state is 7.6 mL/h for nivolumab and 5.5 mL/h for relatlimab. Sex, age, race, and mild hepatic/renal impairment had no clinical effect on clearance. The exposure-response relationship and pharmacodynamic response for the safety and effectiveness of nivolumab/relatlimab-rmbw have not been fully characterized. Safety concerns include severe and fatal immune-mediated adverse reactions, infusion-related reactions, and complications of allogeneic hematopoietic stem cell transplantation, and fetal toxicity. Dosing is determined by patient's age and weight. Solution is infused over a 30-minute timeframe.In the RELATIVITY-047 trial, patients received nivolumab or nivolumab/relatlimab-rmbw. Results showed superiority of dual therapy over monotherapy with a progression-free survival of 10.1 months (95% CI, 6.4-15.7) compared with 4.6 months (95% CI, 3.4-5.6) and hazard ratio of 0.75 (95% CI, 0.62-0.92); P = 0.006, respectively. No safety concerns were observed compared with monotherapy with treatment-related adverse events occurring in 18.9% of patients on combination therapy compared with 9.7% on nivolumab alone.The novel mechanism and improvement in progression-free survival compared with standard of care highlight the therapeutic advancement of nivolumab/relatlimab-rmbw in the treatment of unresectable and metastatic melanoma.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.