抗CD38单抗治疗肾移植晚期抗体介导排斥反应的临床初步探索  

Preliminary clinical exploration of anti-CD38 monoclonal antibody in the treatment of late antibody-mediated rejection after kidney transplantation

作　　者：郭志良 萨如拉 赵大强 郭晖[1] 赵光远 涂宇豪 李松侠 朱兰[1] 陈刚[1] Guo Zhiliang;Sa Rula;Zhao Daqiang;Guo Hui;Zhao Guangyuan;Tu Yuhao;Li Songxia;Zhu Lan;Chen Gang(Institute of Organ Transplantation,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science&Technology,Key Laboratory of Organ Transplantation,Ministry of Education,NHC Key Laboratory of Organ Transplantation,Key Laboratory of Organ Transplantation,Chinese Academy of Medical Sciences,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,器官移植教育部重点实验室,国家卫生健康委员会器官移植重点实验室,中国医学科学院器官移植重点实验室,武汉430030

出　　处：《中华器官移植杂志》2024年第9期622-627,共6页Chinese Journal of Organ Transplantation

基　　金：中国医学科学院中央级公益性科研院所基本科研业务费专项(2023-PT320-07)。

摘　　要：目的初步探索达雷妥尤单抗(Daratumumab)在肾移植晚期抗体介导的排斥反应(late antibody-mediated rejection,late AMR)中的疗效与安全性。方法总结2020年12月至2021年12月在华中科技大学同济医学院附属同济医院接受达雷妥尤单抗治疗肾移植后late AMR的8例受者的临床资料。治疗强化期每周联合血浆置换/静脉注射免疫球蛋白1次加达雷妥尤单抗1次,维持期每2~4周单独静脉滴注达雷妥尤单抗1次。观察治疗前、治疗3个月及治疗12个月时,受者供者特异性抗体(donor-specific antibody,DSA)水平和移植肾功能变化及治疗相关的毒副作用。组间比较采用独立样本T检验。结果8例受者强化期的治疗中位次数为9次,范围在4~17次;维持期治疗时间在5~19个月,其中2例给予5~6次治疗达到抗体清除后停药。8例受者共新生11个位点的DSA。在治疗3个月和12个月时,供者DSA的平均荧光强度分别为6016±4775和6438±3668,均较治疗前的11944±5237明显下降(P=0.012和0.004)。7例受者治疗期间肾功能稳定,1例儿童受者因在治疗期间出现急性排斥反应而在第18个月时恢复血透。7例受者治疗前、治疗3个月、治疗12个月时肾小球滤过率分别为(40.6±20.1)ml·min^(-1)·(1.73m^(2))-1、(53.6±20.9)ml·min^(-1)·(1.73m^(2))-1和(49.0±17.2)ml·min^(-1)·(1.73m^(2))-1,不同时间点比较,差异无统计学意义。有2例受者在输注达雷妥尤单抗早期出现轻微鼻塞症状,余6例在输注过程中无明显不适反应,对药物耐受良好。结论达雷妥尤单抗早期联合血浆置换/静脉输注丙种球蛋白并序贯一定疗程对于降低late AMR受者的抗体具有较好疗效。治疗期间,受者肾功能总体稳定。ObjectiveTo explore the efficacy and safety of daratumumab in late antibody-mediated rejection(late AMR)after kidney transplantation(KT).MethodsFrom December 2020 to December 2021,the relevant clinical data were reviewed for 8 patients with late AMR after receiving daratumumab at Affiliated Tongji Hospital.In intensive phase,the combination of plasma exchange(PP)/intravenous immunoglobulin(IVIG)and daratumumab were dosed once a week;in maintenance phase,once every 2 to 4 weeks.The levels of donor-specific antibody(DSA)and renal function were compared pre-treatment and Month 3/12 post-treatment.The treatment-related toxicities were observed.Independent sample T test was utilized for inter-group comparison.ResultsThe median treatment course during intensive period was 9(4-17)sessions.Maintenance treatment lasted for 5 to 19 months and 2 cases withdrew after 5 to 6 treatments for achieving antibody clearance.A total of 11 DSAs were detected in 8 recipients.At Month 3/12,mean fluorescent intensity(MFI)of DSA was 6016±4775 and 6438±3668.Both were significantly lower than 11944±5237 pre-treatment and the difference was statistically significant(P=0.012,0.004).Seven recipients achieved stable renal function during treatment and one recipient resumed hemodialysis at Month 18 due to acute rejection.Glomerular filtration rate of 7 recipients was(40.6±20.1),(53.6±20.9)and(49.0±17.2)ml·min^(-1)·(1.73 m^(2))-1 pre-treatment and Month 3/12 and no significant differences existed among different timepoints.During follow-ups,2 cases developed mild nasal congestion during an early stage of daratumumab infusion while the remainders had no obvious discomfort during infusion and tolerance was decent.ConclusionEarly combination of daratumumab with PP/IVIG,followed by a course of daratumumab has demonstrated an excellent antibody reduction effect on late AMR.During treatment,renal function remains generally stable.

关 键 词：肾移植 排斥反应 供者特异性抗体 达雷妥尤单抗 

分 类 号：R699.2[医药卫生—泌尿科学]