| 髓外病变和调节T细胞对多发性骨髓瘤嵌合抗原受体T细胞治疗疗效的影响 |
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| 引用本文： | 王佳,翟志敏,葛健,王兴兵,董毅. 髓外病变和调节T细胞对多发性骨髓瘤嵌合抗原受体T细胞治疗疗效的影响[J]. 中国癌症防治杂志, 2022, 14(4): 400-406. DOI: 10.3969/j.issn.1674-5671.2022.04.07 |
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| 作者姓名： | 王佳 翟志敏 葛健 王兴兵 董毅 |
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| 作者单位： | 安徽医科大学第二附属医院血液科；安徽医科大学第一附属医院血液科；中国科学技术大学附属第一医院血液科 |
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| 基金项目： | 安徽省重点研究与开发计划项目（202104j07020030） |
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| 摘 要： | 目的 探讨髓外病变（extramedullary diseases，EMD）和调节T细胞（regulatory T cells，Tregs）对靶向B细胞成熟抗原（B cell mature antigens，BCMA）的嵌合抗原受体T细胞（chimeric antigen receptor T cells，CAR-T）治疗多发性骨髓瘤（relapsed/refractory multiple myeloma，RRMM）疗效的影响。方法 选取2019年6月至2021年9月于安徽医科大学第二附属医院血液科、安徽医科大学第一附属医院血液科、中国科学技术大学附属第一医院血液科接受BCMA?CAR?T治疗的24例RRMM患者为研究对象，输注BCMA?CAR?T细胞后观察和监测治疗反应和毒性；比较有无EMD以及Tregs水平高低组患者的总体缓解率（overall remission rate，ORR）、持续缓解时间（duration of response，DOR）、无复发生存期（relapse?free survival，RFS）和总生存期（overall survival，OS）。结果 RRMM患者输注BCMA?CAR?T细胞2个月内，ORR为87.5%，其中无EMD患者的ORR优于EMD患者（P=0.038），Tregs水平高低不影响患者的ORR（P=0.876）；EMD及Tregs水平异常增高均降低患者的中位DOR（P=0.004，0.001）。EMD患者的OS率和RFS率均低于无EMD患者（60.0％ vs 84.2％，P=0.013；40.0％ vs 57.9％，P=0.007）。Tregs水平异常增高患者的OS率与Tregs水平正常或较低患者比较差异无统计学意义（P=0.077），但RFS率明显降低（40.0％ vs 77.8％，P=0.011）。单因素Cox回归分析结果显示，有EMD患者的OS和RFS均较无EMD患者短（HR=8.465，95%CI：1.150~62.315，P=0.036；HR=5.569，95%CI：1.332~23.285，P=0.019），Tregs水平异常增高患者的RFS也较Tregs水平正常或较低患者短（HR=8.806，95%CI：1.088~71.282，P=0.017）。有无EMD组及Tregs水平高低组患者在BCMA-CAR-T细胞治疗中总体不良事件的发生率差异无统计学意义（均P>0.05）。结论 有EMD的RRMM患者，BCMA?CAR T细胞治疗疗效及生存均较无EMD患者差，异常Tregs可能是其复发的根源之一。
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Effects of extramedullary diseases and regulatory T cells on the treatment efficacy of chimeric antigen receptor T cells in multiple myeloma |
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| WANG Jia,ZHAI Zhimin,GE Jian,WANG Xingbing,DONG Yi. Effects of extramedullary diseases and regulatory T cells on the treatment efficacy of chimeric antigen receptor T cells in multiple myeloma[J]. Journal of Chinese Medical Abstracts·Oncology, 2022, 14(4): 400-406. DOI: 10.3969/j.issn.1674-5671.2022.04.07 |
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| Authors: | WANG Jia ZHAI Zhimin GE Jian WANG Xingbing DONG Yi |
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| Abstract: | Objective To investigate the effects of extramedullary diseases (EMD)and regulatory T cells (Tregs) on the treatment efficacy of B cell mature antigens (BCMA) chimeric antigen receptor T cells (CAR-T) in relapsed/refractory multiple myeloma (RRMM). Methods A total of 24 RRMM patients, who admitted to the Second Affiliated Hospital and the First Affiliated Hospital of Anhui Medical University and the First Affiliated Hospital of the University of Science and Technology of China from June 2019 to September 2021, were selected as the research objects. The treatment response and toxicity were observed and monitored after BCMA-CAR-T cell infusion. The overall remission rate (ORR), duration of response (DOR), follow-up of relapse-free survival (RFS) and overall survival (OS) were compared between the patient groups with and without EMD as well as of high and low Tregs levels. Results Within 2 months of BCMA-CAR-T cell infusion, the ORR of RRMM patients was 87.5%. The ORR of patients without EMD was better than that of patients with EMD (P=0.038), and Tregs levels did not affect the ORR of patients (P=0.876); With EMD and the abnormal increase Tregs reduced the duration of remission ( P=0.004, 0.001).The OS rate and RFS rate of patients with EMD were lower than those without EMD (60.0% vs 84.2%, P=0.013; 40.0% vs 57.9%, P=0.007); The OS rate of patients with abnormally high Tregs level was not significantly different from that of patients with normal or low Tregs level (P=0.077), but the RFS rate was significantly decreased (40.0% vs 77.8%, P=0.011). Univariable Cox regression analysis showed that OS and RFS of patients with EMD were shorter than those without EMD (HR=8.465, 95%CI: 1.150-62.315, P=0.036; HR=5.569, 95%CI: 1.332-23.285, P=0.019), RFS of patients with abnormally high Tregs level was also shorter than that of patients with normal or low Tregs level (HR=8.806, 95%CI: 1.088-71.282, P=0.017). There was no significant difference in the incidence of overall adverse events in BCMA-CAR-T cell therapy between the EMD group and the Tregs group (all P>0.05). Conclusions The efficacy and survival of BCMA-CAR-T cell therapy are worse in RRMM patients with EMD than those without EMD, and abnormal Tregs may be the root causes of its recurrence. |
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| Keywords: | Multiple myeloma B cell mature antigens Chimeric antigen receptor T cells Extramedullary diseases Regulatory T tells Relapsed Refractory |
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