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Patients with myelodysplastic neoplasms (MDS) who progress on hypomethylating agents have poor outcomes [1,2,3]. There are no standard treatment approaches in this setting; while high-dose chemotherapy followed by allogeneic stem cell transplant remains a curative option for higher-risk MDS, advanced age and significant comorbidities preclude this approach for many patients [4].

骨髓增生异常肿瘤（MDS）患者在低甲基化药物方面进展不佳[1，2，3]。在这种情况下没有标准的治疗方法；虽然高剂量化疗后进行同种异体干细胞移植仍然是高风险MDS的治疗选择，但高龄和严重合并症排除了许多患者的这种方法（4）。

In these cases, novel therapies are urgently needed.Programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) are upregulated in hypomethylating agent failure MDS [5]. PD-L1 on the surface of MDS cells binds to PD-1 on T cells, facilitating immune evasion [6]. Similarly, CTLA4 on T cells binds to B7 on MDS cells, stifling T-cell receptor activation and contributing to immune escape [7].

在这些情况下，迫切需要新的疗法。程序性细胞死亡配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA4）在低甲基化剂失败MDS（5）中上调。MDS细胞表面的PD-L1与T细胞上的PD-1结合，促进免疫逃避（6）。类似地，T细胞上的CTLA4与MDS细胞上的B7结合，抑制T细胞受体活化并促进免疫逃逸（7）。

These findings provide a rationale for assessing PD-1 and CTLA4 blockade in MDS following hypomethylating agent exposure [7]. Ipilimumab and nivolumab are fully human IgG1k monoclonal antibodies that target CTLA4 and PD-1, respectively [8, 9]. Both monotherapy and combination immunotherapy approaches are safe and effective in solid tumors and lymphomas; however, their safety and efficacy in relapsed or refractory MDS remains unclear..

这些发现为评估低甲基化剂暴露后MDS中PD-1和CTLA4阻断提供了理论依据（7）。Ipilimumab和nivolumab是分别靶向CTLA4和PD-1的完全人IgG1k单克隆抗体[8，9]。单药治疗和联合免疫治疗方法在实体瘤和淋巴瘤中都是安全有效的；然而，它们在复发或难治性MDS中的安全性和有效性仍不清楚。。

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Fig. 1: Time-to-event analyses of patients w1ho received ipilimumab, nivolumab, or ipilimumab-nivolumab.

图1：接受ipilimumab，nivolumab或ipilimumab-nivolumab的w1ho患者的事件发生时间分析。

Data availability

数据可用性

The data that support the findings of this study are available from the corresponding author upon reasonable request.

根据合理的要求，通讯作者可以提供支持本研究结果的数据。

ReferencesFenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.Article .

参考文献Fenaux P，Mufti GJ，Hellstrom Lindberg E，Santini V，Finelli C，Giagounidis A等。阿扎胞苷与常规治疗方案相比治疗高危骨髓增生异常综合征的疗效：一项随机，开放标签的III期研究。柳叶刀Oncol。2009年；10： 223-32条。

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Jabbour E, Garcia-Manero G, Batty N, Shan J, O’Brien S, Cortes J, et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer. 2010;116:3830–4.Article

Jabbour E，Garcia-Manero G，Batty N，Shan J，O'Brien S，Cortes J等。地西他滨治疗失败后骨髓增生异常综合征患者的预后。癌症。2010年；116:3830–4.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Jabbour EJ, Garcia-Manero G, Strati P, Mishra A, Al Ali NH, Padron E, et al. Outcome of patients with low-risk and intermediate-1-risk myelodysplastic syndrome after hypomethylating agent failure: a report on behalf of the MDS Clinical Research Consortium. Cancer. 2015;121:876–82.Article .

Jabbour EJ，Garcia-Manero G，Strati P，Mishra A，Al-Ali NH，Padron E等。低甲基化药物失败后低风险和中1风险骨髓增生异常综合征患者的预后：代表MDS临床研究联盟的报告。癌症。2015年；121:876-82。文章。

PubMed

PubMed

Google Scholar

谷歌学者

Kadia TM, Jabbour E, Kantarjian H. Failure of hypomethylating agent-based therapy in myelodysplastic syndromes. Semin Oncol. 2011;38:682–92.Article

Kadia TM，Jabbour E，Kantarjian H.骨髓增生异常综合征中低甲基化药物治疗的失败。Semin Oncol公司。2011年；38:682–92.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014;28:1280–8.Article

Yang H，Bueso Ramos C，DiNardo C，Estecio MR，Davanlou M，Geng QR等。低甲基化剂治疗可增强骨髓增生异常综合征中PD-L1，PD-L2，PD-1和CTLA4的表达。白血病。2014年；28:1280–8.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Yang X, Ma L, Zhang X, Huang L, Wei J. Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia. Exp Hematol Oncol. 2022;11:11.Article

Yang X，Ma L，Zhang X，Huang L，Wei J.针对骨髓增生异常综合征和急性髓系白血病中的PD-1/PD-L1途径。Exp Hematol Oncol。2022年；11： 11、条款

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Boddu P, Kantarjian H, Garcia-Manero G, Allison J, Sharma P, Daver N. The emerging role of immune checkpoint based approaches in AML and MDS. Leuk Lymphoma. 2018;59:790–802.Article

Boddu P，Kantarjian H，Garcia-Manero G，Allison J，Sharma P，Daver N.基于免疫检查点的方法在AML和MDS中的新兴作用。白血病淋巴瘤。2018年；59:790–802.Article

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Graziani G, Tentori L, Navarra P. Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Pharm Res. 2012;65:9–22.Article

Graziani G，Tentori L，Navarra P.Ipilimumab：一种用于治疗癌症的新型免疫刺激性单克隆抗体。Pharm Res.2012；65:9–22.文章

CAS

中科院

Google Scholar

谷歌学者

Guo L, Zhang H, Chen B. Nivolumab as Programmed Death-1 (PD-1) Inhibitor for Targeted Immunotherapy in Tumor. J Cancer. 2017;8:410–6.Article

Guo L，Zhang H，Chen B.Nivolumab作为程序性死亡-1（PD-1）抑制剂，用于肿瘤靶向免疫治疗。J癌症。2017年；8： 410-6.文章

CAS

中科院

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zeidan AM, Platzbecker U, Bewersdorf JP, Stahl M, Ades L, Borate U, et al. Consensus proposal for revised International Working Group 2023 response criteria for higher-risk myelodysplastic syndromes. Blood. 2023;141:2047–61.CAS

Zeidan AM，Platzbecker U，Bewersdorf JP，Stahl M，Ades L，Borate U等。修订后的国际工作组2023年高危骨髓增生异常综合征反应标准共识提案。。2023年；141:2047-61.CAS

PubMed

PubMed

Google Scholar

谷歌学者

Thall PF, Sung HG. Some extensions and applications of a Bayesian strategy for monitoring multiple outcomes in clinical trials. Stat Med. 1998;17:1563–80.Article

Thall PF，Sung HG。贝叶斯策略的一些扩展和应用，用于监测临床试验中的多种结果。统计医学1998；17： 1563-80.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)-a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inf. 2009;42:377–81.Article

。研究电子数据捕获（REDCap）-一种元数据驱动的方法和工作流程，用于提供转化研究信息学支持。J生物医学信息2009；42:377-81.文章

Google Scholar

谷歌学者

Harris PA, Taylor R, Minor BL, Elliott V, Fernandez M, O’Neal L, et al. The REDCap consortium: Building an international community of software platform partners. J Biomed Inf. 2019;95:103208.Article

Harris PA，Taylor R，Minor BL，Elliott V，Fernandez M，O'Neal L等。REDCap财团：建立软件平台合作伙伴的国际社区。《生物医学杂志》，2019年；95:103208.文章

Google Scholar

谷歌学者

Chen M, Linstra R, van Vugt M. Genomic instability, inflammatory signaling and response to cancer immunotherapy. Biochim Biophys Acta Rev Cancer. 2022;1877:188661.Article

Chen M，Linstra R，van Vugt M.基因组不稳定性，炎症信号传导和对癌症免疫疗法的反应。Biochim Biophys Acta Rev癌症。2022年；1877:188661.文章

CAS

中科院

PubMed

PubMed

Google Scholar

谷歌学者

Aggarwal C, Ben-Shachar R, Gao Y, Hyun SW, Rivers Z, Epstein C, et al. Assessment of Tumor Mutational Burden and Outcomes in Patients With Diverse Advanced Cancers Treated With Immunotherapy. JAMA Netw Open. 2023;6:e2311181.Article

Aggarwal C，Ben Shachar R，Gao Y，Hyun SW，Rivers Z，Epstein C等。评估免疫治疗的多种晚期癌症患者的肿瘤突变负担和预后。JAMA网络打开。2023年；6： e2311181条

PubMed

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsWe thank Ashli Nguyen-Villarreal, Associate Scientific Editor, in the Research Medical Library at The University of Texas MD Anderson Cancer Center, for editing this article. Study data were collected and managed using REDCap electronic data capture tools hosted at MD Anderson (Project ERIS MDS, version 4.5).

下载参考文献致谢我们感谢德克萨斯大学安德森癌症中心研究医学图书馆的副科学编辑Ashli Nguyen Villarreal编辑本文。使用MD Anderson（Project ERIS MDS，版本4.5）托管的REDCap电子数据捕获工具收集和管理研究数据。

We thank Ashli Nguyen-Villarreal, Associate Scientific Editor, in the Research Medical Library at The University of Texas MD Anderson Cancer Center for editing this article. We thank the patients and their caregivers for their participation in our clinical trials.FundingThis research was funded by the Bristol Myers Squibb Alliance and supported, in part, by the NIH/NCI under award number CA016672 and The University of Texas MD Anderson Cancer Center MDS/AML Moon Shot Program.Author informationAuthors and AffiliationsThe University of Texas MD Anderson Cancer Center, Department of Leukemia, 1515 Holcombe Blvd., Houston, TX, 77030, USAIan M.

我们感谢德克萨斯大学安德森癌症中心研究医学图书馆的副科学编辑Ashli Nguyen Villarreal编辑本文。我们感谢患者及其护理人员参与我们的临床试验。资助该研究由百时美施贵宝联盟资助，部分由NIH/NCI以CA016672号奖项和德克萨斯大学安德森癌症中心MDS/AML Moon Shot计划支持。作者信息作者和附属机构德克萨斯大学MD安德森癌症中心，白血病系，1515 Holcombe Blvd，Houston，TX，77030，USAIan M。

Bouligny, Guillermo Montalban-Bravo, Koji Sasaki, Naval Daver, Elias Jabbour, Yesid Alvarado, Courtney D. DiNardo, Farhad Ravandi, Gautam Borthakur, Naveen Pemmaraju, Tapan Kadia, Lucia Masarova, Koichi Takahashi, Michael Andreeff, Alexandre Bazinet, Hui Yang, Sherry Pierce, Meghan Meyer & Guillermo Garcia-ManeroThe University of Texas MD Anderson Cancer Center, Department of Hematopathology, 1515 Holcombe Blvd., Houston, TX, 77030, USARashmi KanagalThe University of Texas MD Anderson Cancer Center, Department of Biostatistics, 1515 Holcombe Blvd., Houston, TX, 77030, USAXuelin HuangAuthorsIan M.

Bouligny、Guillermo Montalban Bravo、Koji Sasaki、Naval Daver、Elias Jabbour、Yesid Alvarado、Courtney D.DiNardo、Farhad Ravandi、Gautam Borthakur、Naveen Pemmaraju、Tapan Kadia、Lucia Masarova、Koichi Takahashi、Michael Andreeff、Alexandre Bazinet、Hui Yang、Sherry Pierce、Meghan Meyer&Guillermo Garcia Manero德克萨斯大学MD安德森癌症中心血液病理学系，德克萨斯州休斯顿霍尔科姆大道1515号，邮编77030，USARashmi KanagalThe德克萨斯大学MD安德森癌症中心，生物统计学系，1515 Holcombe Blvd，Houston，TX，77030，USAXuelin HuangAuthorsIan M。

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PubMed Google ScholarContributionsIM Bouligny designed the study database, analyzed the data, created the figures, and prepared the manuscript. G Montalban-Bravo enrolled patients and revised the manuscript. K Sasaki enrolled patients and revised the manuscript. N Daver enrolled patients and revised the manuscript.

PubMed Google ScholarContributionsIM Bouligny设计了研究数据库，分析了数据，创建了数字，并准备了手稿。G Montalban Bravo招募了患者并修改了手稿。K Sasaki招募了患者并修改了手稿。。

E Jabbour enrolled patients and revised the manuscript. Y Alvarado enrolled patients and revised the manuscript. CD DiNardo revised the manuscript. F Ravandi enrolled patients and revised the manuscript. G Borthakur enrolled patients and revised the manuscript. N Pemmaraju enrolled patients and revised the manuscript.

E Jabbour招募了患者并修改了手稿。Y Alvarado招募了患者并修改了手稿。CD DiNardo修改了手稿。F Ravandi招募了患者并修改了手稿。G Borthakur招募了患者并修改了手稿。。

T Kadia enrolled patients and revised the manuscript. L Masarova enrolled patients and revised the manuscript. K Takahashi enrolled patients and revised the manuscript. M Andreeff enrolled patients and revised the manuscript. A Bazinet revised the manuscript. H Yang revised the manuscript. R Kanagal interpreted pathology samples and revised the manuscript.

T Kadia招募了患者并修改了手稿。L Masarova招募了患者并修改了手稿。K Takahashi招募了患者并修改了手稿。M Andreeff招募了患者并修改了手稿。。杨修改了手稿。R Kanagal解释了病理样本并修订了手稿。

S Pierce collected data and revised the manuscript. M Meyer obtained patient consent, organized the trial, and revised the manuscript. X Haung assisted with data analysis and revised the manuscript. G Garcia-Manero oversaw the study, enrolled patients, and revised the manuscript.Corresponding authorCorrespondence to.

S Pierce收集了数据并修改了手稿。M Meyer获得了患者的同意，组织了试验，并修改了手稿。X Haung协助数据分析并修改了手稿。G加西亚·马内罗监督了这项研究，招募了患者，并修改了手稿。对应作者对应。

Guillermo Garcia-Manero.Ethics declarations

吉列尔莫·加西亚·马内罗。道德宣言

Competing interests

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The authors declare no competing interests.

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Ethics approval and consent to participate

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The MD Anderson Institutional Review Board approved this study. All patients provided written informed consent according to the Declaration of Helsinki.

MD安德森机构审查委员会批准了这项研究。根据赫尔辛基宣言，所有患者均提供了书面知情同意书。

Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationSupplemental MaterialRights and permissionsSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleBouligny, I.M., Montalban-Bravo, G., Sasaki, K.

。；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Bouligny，I.M.，Montalban Bravo，G.，Sasaki，K。

et al. A phase II trial of ipilimumab, nivolumab, or ipilimumab and nivolumab with or without azacitidine in relapsed or refractory myelodysplastic neoplasms..

等。ipilimumab，nivolumab或ipilimumab和nivolumab联合或不联合阿扎胞苷治疗复发或难治性骨髓增生异常肿瘤的II期临床试验。。

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