Mortezaee Keywan, Majidpoor Jamal
Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran.
Curr Med Chem. 2024 Mar 6. doi: 10.2174/0109298673283943240227104122.
Immunotherapy with immune checkpoint inhibitors (ICIs) is a promising therapeutic schedule in advanced solid cancers. In this review, clinical trials from highly reputable journals are interpreted for safety and efficacy evaluation of the common anti-programmed death-1 (PD-1) inhibitor nivolumab and/or the most known anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor ipilimumab in advanced melanoma. Current progress in the field of melanoma immunotherapy is the focus of this review. Solo nivolumab and combo nivolumab-ipilimumab show higher responses compared to solo ipilimumab or chemotherapy. BRAF and programmed death-ligand 1 (PDL1) expression states are seemingly not reliable biomarkers of response to ICI therapy in melanoma. Solo ipilimumab and particularly a combination of nivolumab-ipilimumab show higher adverse events (AEs) compared with solo nivolumab or chemotherapy. Besides, ICI therapy is safer in mucosal melanoma, but its efficacy is higher in the cutaneous subtype. Patients receiving combination regimens who are experiencing serious AEs can discontinue such regimens until recovery and still maintain clinical benefits. To conclude, combo nivolumab-ipilimumab represents more therapeutic advantages compared with solo nivolumab or ipilimumab, but the rate of AEs is higher for combination regimens. Resistance to combo nivolumab-ipilimumab demands the application of novel approaches to go with ICIs in melanoma immunotherapy. Immunogenic agents, alternative immune checkpoints, vaccination, oncolytic viruses, extracellular vesicles (EVs) and fecal microbiome transplantation (FMT) are novel strategies in patients developing ICI resistance.
使用免疫检查点抑制剂（ICI）进行免疫治疗是晚期实体癌中一种很有前景的治疗方案。在这篇综述中，对来自高声誉期刊的临床试验进行解读，以评估常见的抗程序性死亡-1（PD-1）抑制剂纳武单抗和/或最知名的抗细胞毒性T淋巴细胞相关抗原-4（CTLA-4）抑制剂伊匹单抗在晚期黑色素瘤中的安全性和疗效。黑色素瘤免疫治疗领域的当前进展是本综述的重点。与单独使用伊匹单抗或化疗相比，单独使用纳武单抗以及纳武单抗与伊匹单抗联合使用显示出更高的缓解率。BRAF和程序性死亡配体1（PDL1）的表达状态似乎不是黑色素瘤对ICI治疗反应的可靠生物标志物。与单独使用纳武单抗或化疗相比，单独使用伊匹单抗，尤其是纳武单抗与伊匹单抗联合使用显示出更高的不良事件（AE）发生率。此外，ICI治疗在黏膜黑色素瘤中更安全，但其在皮肤亚型中的疗效更高。接受联合治疗方案且出现严重AE的患者可以停用此类方案直至康复，并且仍能维持临床获益。总之，与单独使用纳武单抗或伊匹单抗相比，纳武单抗与伊匹单抗联合使用具有更多治疗优势，但联合治疗方案的AE发生率更高。对纳武单抗与伊匹单抗联合治疗产生耐药性需要在黑色素瘤免疫治疗中应用新方法与ICI联合使用。免疫原性药物、替代免疫检查点、疫苗接种、溶瘤病毒、细胞外囊泡（EV）和粪便微生物群移植（FMT）是针对发生ICI耐药的患者的新策略。
