Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.
Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.
Blood Rev. 2021 Jan;45:100709. doi: 10.1016/j.blre.2020.100709. Epub 2020 May 23.
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.
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取得了喜忧参半但总体令人失望的结果。然而，对免疫景观、潜在获益生物标志物和耐药机制的认识不断加深，以及合理联合用药的应用和新靶点的确定，都为这一领域带来了充分的乐观前景。在此，我们综述了 ICI 治疗髓系恶性肿瘤的临床前和临床研究的最新进展，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、开发协同且安全的联合疗法，以及确定 ICI 在疾病过程中的最佳应用场景。我们最后展望了这一领域的未来，并提出了一些解决方案，以应对前面提到的主要障碍。
