达雷妥尤单抗联合地塞米松治疗轻链型淀粉样变性肾病疗效及安全性的单中心回顾性分析

Single-center retrospective analysis of efficacy and safety of daratumumab plus dexamethasone for light chain amyloidosis nephropathy

目的分析轻链型淀粉样变性肾病患者使用达雷妥尤单抗联合地塞米松治疗的疗效及安全性,为临床提供参考。方法该研究为单中心回顾性观察研究,回顾性收集2021年12月至2022年8月在浙江大学医学院附属第一医院肾脏病中心接受达雷妥尤单抗联合地塞米松治疗的轻链型淀粉样变性肾病患者治疗前后的临床资料,分析其血液学、肾脏缓解情况以及预后和不良反应。治疗方案为第1天达雷妥尤单抗16 mg/kg静脉滴注+第1~2天地塞米松20 mg静脉推注,每2周1次。随访截止日期为2023年2月28日。结果该研究纳入18例患者,年龄为(58.4±7.7)岁,男女比例为11∶7,11例为初治,7例为经治。根据2012梅奥分期系统,轻链型淀粉样变性Ⅰ、Ⅱ、Ⅲ和Ⅳ期分别为7例、5例、5例和1例。发病前中位病程为2.5(1.0,8.0)个月,随访时间为(8.7±2.8)个月。患者接受治疗次数为(10±3)次。治疗后1、3和6个月血液学总缓解比例分别为9/13、11/13和13/13,非常好的部分缓解及以上比例分别为8/13、10/13和12/13(另5例患者因基线血清游离κ、λ轻链差值<20 mg/L,未细化评估),中位缓解时间为16(13,40)d;3个月、6个月和随访末期肾脏缓解比例分别为10/18、13/18和13/18,中位缓解时间为66(26,182)d。随访过程中,血清游离κ、λ轻链差值中位数降低93%(72%,97%)。至末次随访,1例患者因脏器出血死亡,其他输液反应、白细胞减少、中性粒细胞减少及感染等经对症处理后均好转。结论达雷妥尤单抗联合地塞米松治疗轻链型淀粉样变性肾病可有效清除血液中致病游离轻链,肾脏反应较好,安全性良好.

Objective To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis,and to provide clinical reference.Methods It was a single center retrospective observational study.The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected.The hematologic response,kidney response,prognosis,and adverse events were analyzed.The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1+20 mg intravenous push of dexamethasone on day 1-2,once every 2 weeks.The follow-up was up to February 28,2023.Results The study included 18 patients,with age of(58.4±7.7)years old,and a male to female ratio of 11∶7.Eleven patients were newly diagnosed and 7 patients were retreated.There were 7,5,5 and 1 patients,respectively at the stageⅠ,Ⅱ,ⅢandⅣof light chain amyloidosis according to 2012 Mayo stage criteria.The median course of disease before onset was 2.5(1.0,8.0)months and the follow-up time was(8.7±2.8)months.The patients received(10±3)times of treatment.The overall hematologic response rates were 9/13,11/13 and 13/13 at 1 month,3 months,and 6 months respectively after treatment,meanwhile 8/13,10/13 and 12/13 achieved at least very good partial response at 1 month,3 months,and 6 months respectively(the other 5 patients did not undergo detailed evaluation due to baseline difference of serum freeκandλlight chain<20 mg/L).The median duration of hematologic response was 16(13,40)days.At 3 months,6 months and the end of follow-up,10,13 and 13 of 18 patients respectively achieved renal response,and the median duration of response was 66(26,182)days.During follow-up,the median difference of serum freeκandλlight chain decreased by 93%(72%,97%).Until the last follow-up,one patient died of organ hemorrhage.Other infusion reactions,leukopenia,neutropenia and infection all improved after symptomatic treatments.Conclusion Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission,with good safety.