Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Expert Opin Biol Ther. 2023 May;23(5):383-388. doi: 10.1080/14712598.2023.2215922. Epub 2023 May 24.
Though melanoma is one of the less common skin malignancies, it accounts for the majority of deaths due to cutaneous cancers. The recent progress and drug approvals in targeted treatment and immunotherapy revolutionized the outcome of patients with metastatic disease, and now is also changing the landscape of adjuvant treatment in melanoma.
A combination of anti-PD-1 and anti-CTLA-4 (nivolumab with ipilimumab) has demonstrated superior outcomes in terms of progression-free survival (PFS) and overall survival with recent data confirming median survival exceeding six years. However, the use of this immunotherapy combination is limited in routine practice to approximately half of the patients due to high toxicity with the majority of patients at risk of severe adverse events. The current efforts are to determine how best to integrate combination immunotherapy in different clinical scenarios and limit these drugs' toxicity. That is why novel strategies in immunotherapy are needed and one of the examples of such novelty are anti-LAG-3 antibodies (lymphocyte-activation gene 3). LAG-3 inhibitor (relatlimab) in combination with nivolumab significantly improved PFS as compared to anti-PD-1 monotherapy in patients with previously untreated metastatic or unresectable melanoma. We describe the current status of combination of nivolumab+ relatlimab in the treatment of advanced melanoma patients based on the available data coming from pivotal clinical trials.
The most important question to be answered is what would be the place of this novel combination in the treatment planning strategy.
尽管黑色素瘤是一种较少见的皮肤恶性肿瘤,但它却是导致皮肤癌死亡的主要原因。最近在靶向治疗和免疫治疗方面的进展和药物批准改变了转移性疾病患者的预后,现在也正在改变黑色素瘤辅助治疗的格局。
最近的数据证实,抗 PD-1 和抗 CTLA-4(纳武单抗联合伊匹单抗)联合治疗在无进展生存期(PFS)和总生存期方面的疗效优于其他药物,中位生存期超过六年。然而,由于这种免疫治疗联合方案毒性较高,大多数患者有发生严重不良事件的风险,因此在常规实践中,只有大约一半的患者能够使用这种联合治疗方案。目前的努力是确定如何在不同的临床情况下最好地整合联合免疫治疗,并限制这些药物的毒性。这就是为什么需要新的免疫治疗策略,其中一种新策略是抗 LAG-3 抗体(淋巴细胞激活基因 3)。LAG-3 抑制剂(relatlimab)联合纳武单抗与抗 PD-1 单药治疗相比,可显著改善未经治疗的转移性或不可切除黑色素瘤患者的 PFS。我们根据来自关键临床试验的现有数据,描述了 nivolumab+ relatlimab 联合治疗晚期黑色素瘤患者的现状。
需要回答的最重要的问题是,这种新的联合方案在治疗计划策略中的地位如何。