{"title":"辛替利单抗联合地西他滨治疗高风险、未经治疗的骨髓增生异常综合征：II期单臂试验的疗效、安全性和生物标志物分析。","authors":"Jing Wang, Siqi Li, Hao Jiang, Ying-Jun Chang, Xiaosu Zhao, Jinsong Jia, Xiaolu Zhu, Lizhong Gong, Xiaohong Liu, Wenjing Yu, Xiaojun Huang","doi":"10.1136/jitc-2024-010355","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy combined with azacitidine was feasible in higher-risk myelodysplastic syndromes (MDSs) with limited sample size of treatment-naïve patients, while the optimization of treatment strategies, including the optimal immune checkpoint inhibitor and hypomethylating agent and possible benefiting population, remained undefined. This study first evaluates the efficacy and safety of sintilimab, a PD-1 blockade, plus decitabine in treatment-naïve higher-risk MDS patients and investigates biomarkers for predicting treatment response.</p><p><strong>Methods: </strong>In this phase II, single-arm trial (ChiCTR2100044393), treatment-naïve higher-risk MDS patients with an International Prognostic Scoring System-Revised score >3.5 received sintilimab (200 mg, days 1 and 22) and decitabine (20 mg/m<sup>2</sup>, day 1-5) over 6-week cycles. The primary endpoint was the overall response rate (ORR), including complete remission (CR), partial remission (PR) or marrow CR.</p><p><strong>Results: </strong>A total of 54 eligible patients were enrolled and treated, with 25 (46.3%) having very high-risk MDS. Among 53 evaluable patients, the ORR was 77.4% (n=41), including 26.4% CR (n=14). The overall clinical improvement rate (CR, PR, marrow CR or hematological improvement) reached 81.1%. With a median follow-up of 20.0 months, the median event-free survival was 23 months with 12 progressing to acute myeloid leukemia. Median overall survival was not reached. Treatment was generally well tolerated, with hematologic toxicities being the most common adverse events. Biomarker analysis highlighted a negative correlation between T cell exhaustion markers, particularly TIM-3 and PD-1, with ORR.</p><p><strong>Conclusions: </strong>The combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.</p><p><strong>Trial registration number: </strong>ChiCTR210044393.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"12 11","pages":""},"PeriodicalIF":10.3000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590843/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sintilimab plus decitabine for higher-risk treatment-naïve myelodysplastic syndromes: efficacy, safety, and biomarker analysis of a phase II, single-arm trial.\",\"authors\":\"Jing Wang, Siqi Li, Hao Jiang, Ying-Jun Chang, Xiaosu Zhao, Jinsong Jia, Xiaolu Zhu, Lizhong Gong, Xiaohong Liu, Wenjing Yu, Xiaojun Huang\",\"doi\":\"10.1136/jitc-2024-010355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immunotherapy combined with azacitidine was feasible in higher-risk myelodysplastic syndromes (MDSs) with limited sample size of treatment-naïve patients, while the optimization of treatment strategies, including the optimal immune checkpoint inhibitor and hypomethylating agent and possible benefiting population, remained undefined. This study first evaluates the efficacy and safety of sintilimab, a PD-1 blockade, plus decitabine in treatment-naïve higher-risk MDS patients and investigates biomarkers for predicting treatment response.</p><p><strong>Methods: </strong>In this phase II, single-arm trial (ChiCTR2100044393), treatment-naïve higher-risk MDS patients with an International Prognostic Scoring System-Revised score >3.5 received sintilimab (200 mg, days 1 and 22) and decitabine (20 mg/m<sup>2</sup>, day 1-5) over 6-week cycles. The primary endpoint was the overall response rate (ORR), including complete remission (CR), partial remission (PR) or marrow CR.</p><p><strong>Results: </strong>A total of 54 eligible patients were enrolled and treated, with 25 (46.3%) having very high-risk MDS. Among 53 evaluable patients, the ORR was 77.4% (n=41), including 26.4% CR (n=14). The overall clinical improvement rate (CR, PR, marrow CR or hematological improvement) reached 81.1%. With a median follow-up of 20.0 months, the median event-free survival was 23 months with 12 progressing to acute myeloid leukemia. Median overall survival was not reached. Treatment was generally well tolerated, with hematologic toxicities being the most common adverse events. Biomarker analysis highlighted a negative correlation between T cell exhaustion markers, particularly TIM-3 and PD-1, with ORR.</p><p><strong>Conclusions: </strong>The combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.</p><p><strong>Trial registration number: </strong>ChiCTR210044393.</p>\",\"PeriodicalId\":14820,\"journal\":{\"name\":\"Journal for Immunotherapy of Cancer\",\"volume\":\"12 11\",\"pages\":\"\"},\"PeriodicalIF\":10.3000,\"publicationDate\":\"2024-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590843/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal for Immunotherapy of Cancer\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/jitc-2024-010355\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal for Immunotherapy of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jitc-2024-010355","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Sintilimab plus decitabine for higher-risk treatment-naïve myelodysplastic syndromes: efficacy, safety, and biomarker analysis of a phase II, single-arm trial.
Background: Immunotherapy combined with azacitidine was feasible in higher-risk myelodysplastic syndromes (MDSs) with limited sample size of treatment-naïve patients, while the optimization of treatment strategies, including the optimal immune checkpoint inhibitor and hypomethylating agent and possible benefiting population, remained undefined. This study first evaluates the efficacy and safety of sintilimab, a PD-1 blockade, plus decitabine in treatment-naïve higher-risk MDS patients and investigates biomarkers for predicting treatment response.
Methods: In this phase II, single-arm trial (ChiCTR2100044393), treatment-naïve higher-risk MDS patients with an International Prognostic Scoring System-Revised score >3.5 received sintilimab (200 mg, days 1 and 22) and decitabine (20 mg/m2, day 1-5) over 6-week cycles. The primary endpoint was the overall response rate (ORR), including complete remission (CR), partial remission (PR) or marrow CR.
Results: A total of 54 eligible patients were enrolled and treated, with 25 (46.3%) having very high-risk MDS. Among 53 evaluable patients, the ORR was 77.4% (n=41), including 26.4% CR (n=14). The overall clinical improvement rate (CR, PR, marrow CR or hematological improvement) reached 81.1%. With a median follow-up of 20.0 months, the median event-free survival was 23 months with 12 progressing to acute myeloid leukemia. Median overall survival was not reached. Treatment was generally well tolerated, with hematologic toxicities being the most common adverse events. Biomarker analysis highlighted a negative correlation between T cell exhaustion markers, particularly TIM-3 and PD-1, with ORR.
Conclusions: The combination of sintilimab and decitabine shows promise efficacy for higher-risk MDS, with a favorable safety profile. The potential predictive value of T cell exhaustion biomarkers might help screen the possible benefiting population.
期刊介绍：
The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.
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