贝林妥欧单抗桥接CAR-T细胞疗法治疗成人急性B淋巴细胞白血病疗效及安全性分析  

Clinical efficacy and safety of blinatumomab bridging CAR-T cell therapy in the treatment of patients with adult acute B-cell lymphoblastic leukemia

作　　者：浦妍 周湘粤 刘吟[1] 孔欣 韩晶晶 张剑[1] 林志洪 陈君 仇惠英[1] 吴德沛[1] Pu Yan;Zhou Xiangyue;Liu Yin;Kong Xin;Han Jingjing;Zhang Jian;Lin Zhihong;Chen Jun;Qiu Huiying;Wu Depei(The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology,National Clinical Research Center for Hematologic Diseases,Suzhou 215006,China;Hygeia Suzhou Yongding Hospital,Suzhou 215200,China)

机构地区：[1]苏州大学附属第一医院血液内科,江苏省血液研究所,国家血液系统疾病临床医学研究中心,苏州215006 [2]苏州永鼎医院血液科,苏州215200

出　　处：《中华血液学杂志》2024年第4期339-344,共6页Chinese Journal of Hematology

基　　金：苏州大学自然科学类横向科研项目(H230094);江苏省老年健康科研面上项目(LKM2023015)。

摘　　要：目的探讨贝林妥欧单抗桥接嵌合抗原受体T(CAR-T)细胞疗法治疗急性B淋巴细胞白血病(B-ALL)患者的疗效及安全性。方法回顾性分析2018年8月至2023年5月在苏州大学附属第一医院住院治疗的36例成人B-ALL患者的临床资料。男18例,女18例,中位年龄为43.5(21~72)岁。其中费城染色体阳性急性淋巴细胞白血病(Ph+ALL)21例,复发/难治16例。18例患者接受贝林妥欧单抗桥接CAR-T细胞治疗,18例患者仅接受CAR-T细胞治疗,分析两组患者的疗效及安全性。结果贝林妥欧单抗桥接CAR-T组中16例患者贝林妥欧单抗治疗后获得完全缓解(CR),CR率88.9%。桥接CAR-T治疗1个月后复查骨髓象,CR率为100.0%,微小残留病(MRD)阴性率高于未接受贝林妥欧单抗桥接治疗组(94.4%对61.1%,Fisher,P=0.041)。贝林妥欧单抗桥接CAR-T组患者细胞因子释放综合征(CRS)及其他不良反应发生率低于未接受贝林妥欧单抗桥接治疗组(11.1%对50.0%,Fisher,P=0.027)。截至随访终点,贝林妥欧单抗桥接CAR-T组中13例患者持续MRD阴性状态,5例患者(包含2例经贝林妥欧单抗治疗无效的病例)在治疗后2.57~10.20个月复发,2例复发患者后续接受第二次CAR-T细胞治疗后达CR。未接受贝林妥欧单抗桥接治疗组中10例患者持续MRD阴性状态,7例复发,6例死亡。贝林妥欧单抗桥接CAR-T组患者1年总生存率高于未接受桥接治疗组,差异在0.1水平有统计学意义[(88.9±10.5)%对(66.7±10.9)%,P=0.091]。结论贝林妥欧单抗桥接CAR-T细胞治疗成人B-ALL疗效及安全性值得肯定,清除肿瘤残留效果好,近期疗效复发率低,不良反应少。Objective Exploring the efficacy and safety of bridging blinatumomab(BiTE)in combination with chimeric antigen receptor T(CAR-T)cell therapy for the treatment of adult patients with acute B-cell lymphoblastic leukemia(B-ALL).Methods Clinical data from 36 adult B-ALL patients treated at the First Affiliated Hospital of Suzhou University from August 2018 to May 2023 were retrospectively analyzed.A total of 36 cases were included:18 men and 18 women.The median age was 43.5 years(21-72 years).Moreover,21 cases of Philadelphia chromosome-positive acute lymphoblastic leukemia were reported,and 16 of these cases were relapsed or refractory.Eighteen patients underwent blinatumomab bridging followed by CAR-T cell therapy,and 18 patients received CAR-T cell therapy.This study analyzed the efficacy and safety of treatment in two groups of patients.Results In the BiTE bridge-to-CAR-T group,16 patients achieved complete remission(CR)after BiTE immunotherapy,with a CR rate of 88.9%.One month after bridging CAR-T therapy,bone marrow examination showed a CR rate of 100.0%,and the minimal residual disease(MRD)negativity rate was higher than the nonbridging therapy group(94.4%vs.61.1%,Fisher,P=0.041).The incidence of cytokine release syndrome and other adverse reactions in the BiTE bridge-to-CAR-T group was lower than that in the nonbridging therapy group(11.1%vs.50.0%,Fisher,P=0.027).The follow-up reveals that 13 patients continued to maintain MRD negativity,and five patients experienced relapse 8.40 months(2.57-10.20 months)after treatment.Two of five patients with relapse achieved CR after receiving the second CAR-T cell therapy.In the nonbridging therapy group,10 patients maintained continuous MRD negativity,7 experienced relapse,and 6 died.The 1 year overall survival rate in the BiTE bridge-to-CAR-T group was higher than that in the nonbridging therapy group,with a statistically significant difference at the 0.1 level(88.9%±10.5%vs.66.7%±10.9%,P=0.091).Conclusion BiTE bridging CAR-T cell therapy demonstrates excellent effic

关 键 词：贝林妥欧单抗 嵌合抗原受体T细胞 急性B淋巴细胞白血病 抗肿瘤免疫治疗方案 微小残留病 

分 类 号：R733.71[医药卫生—肿瘤]