Tsumura Aaron, Levis Daniel, Tuscano Joseph M
Division of Malignant Hematology/Cellular Therapy and Transplantation, University of California Davis, Sacramento, CA, United States.
School of Medicine, University of California Davis, Sacramento, CA, United States.
Front Oncol. 2023 Oct 17;13:1288172. doi: 10.3389/fonc.2023.1288172. eCollection 2023.
Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.
检查点抑制剂疗法已成为多种恶性肿瘤的有效治疗策略,尤其是在实体瘤中。在过去二十年中,许多靶向CTLA-4和PD-1/PD-L1检查点通路的单克隆抗体药物已获得美国食品药品监督管理局(FDA)批准。在血液系统恶性肿瘤中,霍奇金淋巴瘤迄今为止已获得最大的临床益处,最新数据显示其在一线治疗中有效。随着我们对检查点抑制的理解不断扩展,将这些通路作为治疗靶点在其他血液系统恶性肿瘤的治疗中也显示出一定作用,主要用于复发/难治性情况。检查点抑制似乎还可作为一种增效剂,增强对其他形式治疗(如造血干细胞移植)的临床反应。此外,绕过已被充分研究的CTLA-4和PD-1/PD-L1通路的替代性检查点分子已成为令人兴奋的新治疗靶点。最令人兴奋的是抗CD47阻断剂在治疗高危骨髓增生异常综合征(MDS)和TP-53突变的急性髓系白血病(AML)中的应用。总体而言,在理解检查点抑制在血液系统恶性肿瘤中的益处方面已取得巨大进展,但在所有领域都需要进一步研究,以最佳利用这些药物。本文综述了过去十年血液系统恶性肿瘤免疫检查点抑制的最新进展。