scholarly journals Meta-Analysis of Interleukin-2 Receptor Antagonists as the Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Meng-Zhu Shen ◽  
Jing-Xia Li ◽  
Xiao-Hui Zhang ◽  
Lan-Ping Xu ◽  
Yu Wang ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Response Rate ◽  
Meta Analysis ◽  
Interleukin 2 ◽  
Efficacy And Safety ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft ◽  
Better Than

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (HSCT). Corticosteroid is the first-line treatment for aGVHD, but its response rate is only approximately 50%. At present, no uniformly accepted treatment for steroid-refractory aGVHD (SR-aGVHD) is available. Blocking interleukin-2 receptors (IL-2Rs) on donor T cells using pharmaceutical antagonists alleviates SR-aGVHD. This meta-analysis aimed to compare the efficacy and safety of four commercially available IL-2R antagonists (IL-2RAs) in SR-aGVHD treatment. A total of 31 studies met the following inclusion criteria (1): patients of any race, any sex, and all ages (2); those diagnosed with SR-aGVHD after HSCT; and (3) those using IL-2RA-based therapy as the treatment for SR-aGVHD. The overall response rate (ORR) at any time after treatment with basiliximab and daclizumab was 0.81 [95% confidence interval (CI): 0.74–0.87)] and 0.71 (95% CI: 0.56–0.82), respectively, which was better than that of inolimomab 0.54 (95% CI: 0.39–0.68) and denileukin diftitox 0.56 (95% CI: 0.35–0.76). The complete response rate (CRR) at any time after treatment with basiliximab and daclizumab was 0.55 (95% CI: 0.42–0.68) and 0.42 (95%CI: 0.29–0.56), respectively, which was better than that of inolimomab 0.30 (95% CI: 0.16–0.51) and denileukin diftitox 0.37 (95% CI: 0.24–0.52). The ORR and CRR were better after 1-month treatment with basiliximab and daclizumab than after treatment with inolimomab and denileukin diftitox. The incidence of the infection was higher after inolimomab treatment than after treatment with the other IL-2RAs. In conclusion, the efficacy and safety of different IL-2RAs varied. The response rate of basiliximab was the highest, followed by that of daclizumab. Prospective, randomized controlled trials are needed to compare the efficacy and safety of different IL-2RAs.

Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Blood ◽  
2004 ◽  
Vol 104 (4) ◽  
pp. 1224-1226 ◽  
Author(s):  
Vincent T. Ho ◽  
David Zahrieh ◽  
Ephraim Hochberg ◽  
Eileen Micale ◽  
Jesse Levin ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Phase 1 ◽  
Interleukin 2 ◽  
Maximum Tolerated Dose ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Denileukin Diftitox ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 μg/kg intravenously on days 1 and 15; 18 received 9 μg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 μg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD. (Blood. 2004;104:1224-1226)

Efficacy of the interleukin-2 receptor antagonist basiliximab in steroid-refractory acute graft-versus-host disease

2005 ◽  
Vol 130 (4) ◽  
pp. 568-574 ◽  
Author(s):  
Martin Schmidt-Hieber ◽  
Thomas Fietz ◽  
Wolfgang Knauf ◽  
Lutz Uharek ◽  
Werner Hopfenmuller ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Graft Versus Host Disease ◽  
Interleukin 2 ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interleukin 2 Receptor ◽  
Steroid Refractory ◽  
Acute Graft

scholarly journals Efficacy and Safety of Ruxolitinib in Treatment of Steroid Refractory/Refractory Acute Graft-Versus-Host Disease: A Prospective Multicenter Research

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5724-5724
Author(s):  
Zhiping Fan ◽  
Lan Deng ◽  
Xudong Li ◽  
Qing Zhang ◽  
Li Xuan ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Conflicts Of Interest ◽  
Bleeding Tendency ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory ◽  
Acute Graft

Abstract Objectives To explore the efficacy and safety of ruxolitinib in the treatment of steroid refractory/refractory acute graft versus host disease (aGVHD). Methods A prospective analysis was conducted in the 31 steroid refractory/refractory aGVHD cases who treated with ruxolitinib from October 2017 to June 2018. The first dose of ruxolitinib was 5-10mg bid, and the dose was adjusted to 5mg qd for maintenance treatment when complete remission (CR) status lasted for 2 weeks after steroid refractory/refractory aGVHD turned into CR. Results Of all the 29 steroid refractory/refractory aGVHD patients, 15 patients were treated with ruxolitinib in case of disease progression after receiving at least one second-line treatment, and 14 cases directly with ruxolitinib after the occurrence of corticosteroid refractoriness. The time of starting ruxolitinib treatment after the occurrence of aGVHD was 10 (4-81) d, the median time of onset was 8 (3-18) d. The overall response rate was 89.6% (26/29) including 22 complete responses (75.9%), and 4 partial responses (13.8%). 12 patients with thrombocytopenia need to reduce the dose of ruxolitinib, and 1 patient withdrew treatment for obvious bleeding tendency. With the median follow-up 3 (2-8) months after treatment with ruxolitinib, 28 patients survived and 1 died of severe pneumonia related to aGVHD, and the overall survival was 96.6% (28/29). Conclusion Ruxolitinib is safe and effective in the treatment of steroid refractory/refractory aGVHD, and can be used as a second-line treatment for refractory aGVHD. Disclosures No relevant conflicts of interest to declare.

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