Blood Reviews ( IF 7.4 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.blre.2020.100709 Jan Philipp Bewersdorf 1 , Rory M Shallis 1 , Amer M Zeidan 1
Immune checkpoint inhibitors (ICI) have yielded mixed but largely underwhelming results in clinical trials in patients with acute myeloid leukemia and myelodysplastic syndromes to date. However, increasing understanding of the immunologic landscape, potential biomarkers for benefits, and mechanisms of resistance, as well as the use of rational combinations, and identification of novel targets leaves plenty of room for optimism. Herein, we review recent advances in the preclinical and clinical development of ICI therapy in patients with myeloid malignancies and explore some of the important challenges facing the field such as the absence of validated biomarkers, the development of synergistic and safe combination therapies, and efforts to determine the best setting of ICI along the disease course. We finally foresee the future of the field and propose solutions to some of the major beforementioned obstacles.
中文翻译:
髓系恶性肿瘤中的免疫检查点抑制:超越 PD-1/PD-L1 和 CTLA-4 通路
迄今为止,免疫检查点抑制剂 (ICI) 在急性髓系白血病和骨髓增生异常综合征患者的临床试验中产生了混合但很大程度上平庸的结果。然而,随着对免疫学领域、潜在益处的生物标志物和耐药机制的了解越来越多,以及合理组合的使用和新靶点的识别,人们仍有很大的乐观空间。在此,我们回顾了髓系恶性肿瘤患者 ICI 治疗的临床前和临床开发的最新进展,并探讨了该领域面临的一些重要挑战,例如缺乏经过验证的生物标志物、协同和安全的联合疗法的开发以及努力确定病程中 ICI 的最佳设置。