Efficacy and safety of human umbilical cord-derived mesenchymal stem cells versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease: a multicentre, randomized, double-blind, phase 2 trial.

Autor: Jiang E; School of Medicine, Nankai University, Nankai District, 94 Weijin Road, Tianjin, 300071, China.; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300041, China., Qian K; School of Medicine, Nankai University, Nankai District, 94 Weijin Road, Tianjin, 300071, China.; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China., Wang L; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China., Yang D; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300041, China., Shao Y; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China., Hu L; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China., Li Y; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China., Yao C; Peking University Clinical Research Institute, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China., Han M; State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, 288 Nanjing Road, Heping District, Tianjin, 300041, China. mzhan@ihcams.ac.cn., Hou X; Platinumlife Biotechnology (Beijing) Co., Ltd, Beijing Economic-Technological Development Area, 8 Ruihe Road, Beijing, 100176, China. houxiaoqiang@platinumlife.cn., Liu D; School of Medicine, Nankai University, Nankai District, 94 Weijin Road, Tianjin, 300071, China. daihongrm@163.com.; Department of Hematology, theFifth Medical Center of ChineseFengtai District, PLA General Hospital, 8 East Street, Beijing, 100071, China. daihongrm@163.com.
Jazyk: angličtina
Zdroj: BMC medicine [BMC Med] 2024 Nov 25; Vol. 22 (1), pp. 555. Date of Electronic Publication: 2024 Nov 25.
DOI: 10.1186/s12916-024-03782-5
Abstrakt: Background: Failure of systemic corticosteroid therapy is common in patients with newly diagnosed acute graft-versus-host disease (aGVHD) above grade II. Mesenchymal stem cells (MSCs) have been used as a tolerable and potentially effective second-line therapy for steroid-refractory aGVHD (SR-aGVHD); however, well-designed, prospective, controlled studies are lacking.
Methods: This multicentre, randomized, double-blind, placebo-controlled, exploratory phase 2 study enrolled patients with SR-aGVHD above grade II from 7 centres. Patients were randomized 1:1 to receive umbilical cord-derived MSCs or placebo added to one centre's choice of second-line agents (except for ruxolitinib). The agents were infused twice weekly. Patients with complete response (CR), no response (NR), or progression of disease (PD) at d28 received 8 infusions, and those with partial response (PR) received the above infusions for another 4 weeks. The per-protocol population consisted of patients who received ≥ 8 infusions. The primary endpoint was the overall response rate (ORR, CR + PR) at d28, analyzed in the per-protocol and intention-to-treat populations.
Results: Seventy-eight patients (median age 38, range 13-62) were enrolled: 40 in the MSC group and 38 in the control. Patients in the MSC group received a median of 8 doses, with a median response time of 14 days. In intention-to-treat analysis, ORR at d28 was 60% for MSC group and 50% for control group (p = 0.375). The 2-year cumulative incidence of moderate to severe cGVHD was marginally lower in the MSC group than in the control (13.8% vs. 39.8%, p = 0.067). The 2-year failure-free survival was similar between the MSC and control groups (52.5% vs. 44.4%, p = 0.43). In per-protocol analysis (n = 62), ORR at d28 was significantly greater in the MSC group than in the control group (71.9% vs. 46.7%, p = 0.043). Among patients with gut involvement, ORR at d28 was significantly greater in the MSC group than in the control (66.7% vs. 33.3%, p = 0.031). The adverse events incidences were similar between groups.
Conclusions: In this exploratory study, there was no superior ORR at d28 demonstrated in the MSC group compared with the control. However, MSCs showed a gradual treatment effect at a median of 2 weeks. Patients who completed 8 infusions may benefit from adding MSCs to one conventional second-line agent, especially those with gut involvement. MSCs was well tolerated in patients with SR-aGVHD.
Trial Registration: chictr.org.cn ChiCTR2000035740.
Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Ethics Committee of the General Hospital of the Chinese People’s Liberation Army (C2020-016–05). Patient’s written consent to participate in this clinical trial was obtained prior to any study-specific procedures. Consent for publication: Not applicable. Competing interests: X.H. is an employee of Platinumlife Biotechnology (Beijing). The other authors have no conflicts of interest to report.
(© 2024. The Author(s).)
Databáze: MEDLINE
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