Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Ann Hematol. 2020 Apr;99(4):847-853. doi: 10.1007/s00277-020-03968-w. Epub 2020 Feb 21.
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.
慢性移植物抗宿主病(cGvHD)仍然是影响异基因造血干细胞移植(alloHSCT)后生存的最相关因素。除皮质类固醇(和美国的伊布替尼)外,cGvHD 尚无既定的治疗方法。托珠单抗是一种人源化 IgG1IL6 受体抗体,已显示出在急性 GvHD 和 cGvHD 中的疗效。我们回顾性分析了托珠单抗治疗晚期 cGvHD 的疗效和安全性。11 例患有严重类固醇难治性 cGvHD 的患者(中位年龄 49 岁;范围 21-62 岁)接受了至少两线 cGvHD 治疗(范围 2-8 个方案),接受了托珠单抗(q4w,剂量 8mg/kg IV)治疗,中位治疗周期数为 15 个(范围 2-31 个)。在开始托珠单抗治疗之前和治疗后 3、6 和 12 个月记录了 cGvHD 的 NIH 共识标准分级。所有患者均接受了额外的联合免疫抑制(IS)治疗,但在开始托珠单抗治疗前的最后 4 周内未使用新的 IS,并且在开始任何新的 IS 之前终止了反应评估。从 alloHSCT 到开始托珠单抗治疗的中位天数为 1033 天。开始托珠单抗治疗时受累的器官为皮肤(100%,均为 3 级)、眼睛(82%)、筋膜(82%)、口腔(64%)、肺(55%)和生殖器(18%)。总体而言,7/10 例患者(70%)出现部分缓解,2/10 例患者(20%)出现进行性 cGvHD,1/10 例患者(10%)出现混合反应,1 例患者在开始治疗后 1.5 个月因败血症在首次反应评估前死亡。4 例患者需要后续新的免疫抑制治疗。2 例患者发生细菌性败血症,其中 1 例死亡。在平均随访 22 个月(范围 1.5-52 个月)的情况下,总生存率和无复发生存率分别为 82%。托珠单抗似乎是晚期 cGvHD 的一种有前途的治疗选择,但需要在 II 期试验中进一步评估。