复发难治多发性骨髓瘤患者接受BCMACAR-T治疗后血细胞减少的特征及对预后的影响  

The characteristics and impact on prognosis of cytopenia after anti-BCMA-CAR-T therapy in patients with relapsed and refractory multiple myeloma

作　　者：沈旭星 姚叶 夏园 金媛媛 张闰[1] 李建勇[1] 陈丽娟[1] Shen Xuxing;Yao Ye;Xia Yuan;Jin Yuanyuan;Zhang Run;Li Jianyong;Chen Lijuan(Department of Hematology,the First Affiliated Hospital of Nanjing Medical University,Jiangsu Province Hospital,Nanjing 210029,China;Department of Hematology,the Affiliated Taizhou People's Hospital of Nanjing Medical University,Taizhou School of Clinical Medicine,Taizhou 225300,China)

机构地区：[1]南京医科大学第一附属医院,江苏省人民医院血液科,南京210029 [2]南京医科大学附属泰州人民医院血液科,泰州225300

出　　处：《中华医学杂志》2024年第7期507-513,共7页National Medical Journal of China

基　　金：国家自然科学基金(82370205、82200223);江苏省科技计划专项资金社会发展项目(BE2022810);南京医科大学泰州临床医学院重点项目(TZKY20220310);江苏省科技计划专项(基础研究计划自然科学基金)(BK20220718)

摘　　要：目的探讨复发难治多发性骨髓瘤(RRMM)患者接受B细胞成熟抗原(BCMA)嵌合抗原受体T细胞(CAR-T)治疗后血细胞减少的特征及对预后的影响。方法回顾性收集2017年4月至2023年3月南京医科大学第一附属医院接受BCMA CAR-T治疗的36例RRMM患者的临床资料,其中男17例,女19例,年龄[M(Q_(1),Q_(3))]为62(53,67)岁。随访截至2023年8月31日,随访时间[M(Q_(1),Q_(3))]为33(10,30)个月。分析所有患者清除淋巴细胞前、CAR-T回输后不同时间点的血细胞减少特征。采用Kaplan-Meier法绘制生存曲线,比较不同临床特征患者无进展生存时间(PFS)及总生存时间(OS)的差异;采用单细胞测序分析其中3例患者CAR-T治疗后造血干细胞变化特征。结果36例RRMM患者接受BCMA CAR-T治疗后血细胞减少发生率达100%。中性粒细胞减少发生率在回输后第7天[全部等级中性粒细胞减少占61.1%(22/36),≥3级中性粒细胞减少占33.3%(12/36)]和第28天[全部等级中性粒细胞减少占67.9%(19/28),≥3级中性粒细胞减少占28.6%(8/28)]呈现峰值,呈双相型变化(P<0.001)。淋巴细胞减少在回输当天即达高峰[全部等级淋巴细胞减少占97.2%(35/36),≥3级淋巴细胞减少占80.6%(29/36)](P<0.001)。全部等级血小板减少和重度血小板减少(≥3级)的发生率在回输后第14天达到高峰,分别为69.4%(25/36)、30.6%(11/36),且持续时间长(P<0.001);回输后12个月仍有40%(8/20)患者发生血小板减少。贫血发生率在回输后第7、14天达到高峰,为100%(36/36),恢复缓慢(P<0.001);回输后12个月仍有50%(10/20)患者发生贫血。Kaplan-Meier生存分析显示,血小板减少<3级患者的OS为未达到,血小板减少≥3级患者的OS缩短[17(95%CI:2~32)个月,χ^(2)=4.154,P=0.042],预后较差;而其他血细胞减少和生存的关系差异均无统计学意义(均P>0.05)。骨髓单细胞测序分析发现CAR-T回输后造血干细胞增殖减少、凋亡增加、细胞周期受阻。结论所有患者在接Objective To investigate the characteristics of cytopenia and its impact on prognosis in patients with relapsed and refractory multiple myeloma(RRMM)after B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)immunotherapy therapy.Methods Clinical data of 36 RRMM patients received BCMA CAR-T therapy at the First Affiliated Hospital of Nanjing Medical University from April 2017 to March 2023 were retrospectively collected.Among them,there were 17 males and 19 females,with an age[M(Q_(1),Q_(3))]of 62(53,67)years.The follow-up deadline was August 31,2023,and the follow-up time[M(Q_(1),Q_(3))]was 33(10,30)months.The characteristics of cytopenia at different time points before lymphodepleting chemotherapy and after CAR-T cell infusion in all patients were analyzed.Kaplan-Meier method was used to compare the differences in progression-free survival(PFS)and overall survival(OS)in patients with different clinical characteristics.Single-cell sequencing analysis was used to analyze the changes in hematopoietic stem cells in three patients after CAR-T cell therapy.Results The incidence of cytopenia after BCMA CAR-T cell therapy in 36 RRMM patients reached 100%.The incidence of neutropenia peaked on the 7th and 28th day after cell infusion with a biphasic pattern of change.Patients with all grade neutropenia reached 61.1%(22/36)and grade 3 or higher reached 33.3%(12/36)on the 7th day,while patients with all grade neutropenia reached 67.9%(19/28)and grade 3 or higher reached 28.6%(8/28)on the 28th day(P<0.001),respectively.The occurrence rate of lymphopenia reached a peak on the day of CAR-T cell infusion[97.2%(35/36)patients showed lymphopenia,while 80.6%(29/36)patients showed grade 3 or higher lymphopenia](P<0.001).The incidence of all grade of thrombocytopenia and severe thrombocytopenia(grade 3 or higher)peaked on the 14th day after cell infusion,with the rates of 69.4%(25/36)and 30.6%(11/36)respectively,which had a prolonged duration(P<0.001).Even after 12 months,40%(8/20)of patients still experienced thr

关 键 词：多发性骨髓瘤 B细胞成熟抗原 嵌合抗原受体T细胞 血细胞减少 随访研究 

分 类 号：R733.3[医药卫生—肿瘤]