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IL6-receptor antibody tocilizumab as salvage therapy in severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a retrospective analysis.
Annals of Hematology ( IF 3.5 ) Pub Date : 2020-02-21 , DOI: 10.1007/s00277-020-03968-w
Anna-Sophia Kattner 1 , Ernst Holler 1 , Barbara Holler 1 , Sebastian Klobuch 1 , Daniela Weber 1 , Danilo Martinovic 1 , Matthias Edinger 1 , Wolfgang Herr 1 , Daniel Wolff 1
Affiliation  

Chronic graft-versus-host disease (cGvHD) remains the most relevant factor affecting survival after allogeneic hematopoietic stem cell transplantation (alloHSCT). Besides corticosteroids (and ibrutinib in the USA), there is no established therapy for cGvHD. Tocilizumab, a humanized IgG1 IL6-receptor antibody, has shown efficacy in acute GvHD and cGvHD. We retrospectively analyzed the efficacy and safety of tocilizumab for the treatment of advanced cGvHD. Eleven patients with severe steroid refractory cGvHD (median age 49; range 21-62 years) that received at least two prior lines of therapy for cGvHD (range 2-8 regimens) were treated with tocilizumab (q4w, dosage 8 mg/kg IV) with a median number of 15 cycles (range 2-31). NIH consensus criteria grading for cGvHD were recorded prior to tocilizumab administration and after 3, 6, and 12 months of therapy. All patients received additional concomitant immunosuppression (IS) but no new IS within the last 4 weeks before start of tocilizumab and response assessment was terminated before start of any new IS. The median number of days between alloHSCT and initiation of tocilizumab therapy was 1033 days. Organs involved at initiation of tocilizumab therapy were skin (100%, all grade 3), eyes (82%), fascia (82%), mouth (64%), lungs (55%), and genitals (18%). Overall, 7/10 patients (70%) showed partial remission, 2/10 patients (20%) showed progressive cGvHD, 1/10 patient (10%) showed mixed response, and 1 patient died due to sepsis before first response assessment 1.5 months after initiation of treatment. Four patients required subsequent new immunosuppressive treatment. Two patients developed bacterial sepsis, one of whom died. The overall survival and relapse-free survival were 82% with an average follow-up of 22 months (range 1.5-52 months). Tocilizumab seems a promising treatment option in advanced cGvHD but further evaluation within a phase II trial is required.

中文翻译:

异基因造血干细胞移植后重度慢性移植物抗宿主病的IL6-受体抗体tocilizumab抢救治疗:回顾性分析。

慢性移植物抗宿主病(cGvHD)仍然是同种异体造血干细胞移植(alloHSCT)后影响存活率的最重要因素。除了皮质类固醇(和美国的依鲁替尼)外,尚无针对cGvHD的成熟疗法。人源化IgG1 IL6-受体抗体Tocilizumab在急性GvHD和cGvHD中显示出功效。我们回顾性分析了托珠单抗治疗晚期cGvHD的疗效和安全性。接受至少两次先前的cGvHD治疗方案(范围2-8方案)的重度类固醇难治性cGvHD重症患者(中位年龄49;范围21-62岁)用托珠单抗(q4w,剂量8 mg / kg静脉注射)治疗中位数为15个周期(范围为2-31)。在给予托珠单抗之前,3、6之后记录了cGvHD的NIH共识标准等级。和12个月的治疗。所有患者均接受了额外的伴随免疫抑制(IS),但在开始tocilizumab前的最后4周内没有新的IS,并且在开始任何新的IS之前终止了反应评估。从alloHSCT到开始tocilizumab治疗之间的中位数天数为1033天。开始使用tocilizumab涉及的器官是皮肤(100%,所有3级),眼睛(82%),筋膜(82%),口(64%),肺(55%)和生殖器(18%)。总体而言,有7/10例患者(70%)表现出部分缓解,2/10例患者(20%)表现为进行性cGvHD,1/10例患者(10%)表现出混合反应,1例患者在首次反应评估前因败血症死亡1.5开始治疗后的几个月。四名患者需要随后的新的免疫抑制治疗。两名患者出现细菌性败血症,其中一名死亡。总体生存和无复发生存率为82%,平均随访22个月(范围1.5-52个月)。在晚期cGvHD中,Tocilizumab似乎是一种有前途的治疗选择,但需要在II期临床试验中进行进一步评估。
更新日期:2020-02-21
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