Alfayez Mansour, Borthakur Gautam
a Department of Leukemia , University of Texas M. D. Anderson Cancer Center , Houston , TX , USA.
Expert Rev Hematol. 2018 May;11(5):373-389. doi: 10.1080/17474086.2018.1459184.
Immunity, for treatment of acute myelogenous leukemia (AML), has been leveraged historically in the form of allogeneic stem cell transplantation. Checkpoint inhibitors (CPI) as positive modulators of immune response have been recent major breakthroughs in solid tumors. Areas covered: Emerging concepts and clinical data with CPIs in acute Myeloid Leukemia - the focus of this review- will be discussed. CPIs can potentially be effective in absence of 'actionable' mutations and are expected to be effective against poor-risk AML. Immune inhibitory checkpoint molecules are upregulated in both de novo and relapsed AML. Similar data also suggest role of checkpoint molecules in mediating resistance particularly to hypomethylating agent (HMA) therapy, which can potentially be reversed by using checkpoint inhibitors. Expert commentary: Ongoing clinical trials in combination with HMAs are showing early promise, with doubling of response than that seen in historic controls. The optimal combinations of CPIs and the optimal space that they will fit in the continuum of AML therapies need lot of in depth work.
在急性髓系白血病（AML）的治疗中，免疫疗法一直以来都以异基因干细胞移植的形式被应用。作为免疫反应阳性调节剂的检查点抑制剂（CPI）是实体瘤领域近期的重大突破。涵盖领域：本文将讨论急性髓系白血病中与检查点抑制剂相关的新兴概念和临床数据，这也是本综述的重点。在没有“可操作”突变的情况下，检查点抑制剂可能有效，并且有望对高危AML有效。免疫抑制检查点分子在初发和复发的AML中均上调。类似数据也表明检查点分子在介导耐药性中发挥作用，尤其是对低甲基化剂（HMA）治疗的耐药，而使用检查点抑制剂可能会逆转这种耐药。专家评论：与HMA联合进行的正在进行的临床试验显示出早期前景，与历史对照相比，缓解率提高了一倍。检查点抑制剂的最佳组合以及它们在AML治疗连续过程中最合适的应用空间需要大量深入研究。
