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Meta-Analysis
. 2023 Jun 20:14:1211171.
doi: 10.3389/fimmu.2023.1211171. eCollection 2023.

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

Chengxin Luo  1   2 , Xiangtao Huang  1   2 , Ling Wei  1   2 , Guixian Wu  1   2 , Yarui Huang  1   2 , Yaqun Ding  1   2 , Zhen Huang  1   2 , Jieping Chen  1   2 , Xi Li  3 , Yunding Zou  1   2 , Shuangnian Xu  1   2
Affiliations
Meta-Analysis

Second-line therapy for patients with steroid-refractory aGVHD: systematic review and meta-analysis of randomized controlled trials

Chengxin Luo et al. Front Immunol. .

Abstract

Objective: Steroids-refractory (SR) acute graft-versus-host disease (aGVHD) is a life-threatening condition in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the optimal second-line therapy still has not been established. We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of different second-line therapy regimens.

Methods: Literature search in MEDLINE, Embase, Cochrane Library and China Biology Medicine databases were performed to retrieve RCTs comparing the efficacy and safety of different therapy regimens for patients with SR aGVHD. Meta-analysis was conducted with Review Manager version 5.3. The primary outcome is the overall response rate (ORR) at day 28. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated with the Mantel-Haenszel method.

Results: Eight eligible RCTs were included, involving 1127 patients with SR aGVHD and a broad range of second-line therapy regimens. Meta-analysis of 3 trials investigating the effects of adding mesenchymal stroma cells (MSCs) to other second-line therapy regimens suggested that the addition of MSCs is associated with significantly improvement in ORR at day 28 (RR = 1.15, 95% CI = 1.01-1.32, P = 0.04), especially in patients with severe (grade III-IV or grade C-D) aGVHD (RR = 1.26, 95% CI = 1.04-1.52, P = 0.02) and patients with multiorgan involved (RR = 1.27, 95% CI = 1.05-1.55, P = 0.01). No significant difference was observed betwwen the MSCs group and control group in consideration of overall survival and serious adverse events. Treatment outcomes of the other trials were comprehensively reviewed, ruxolitinib showed significantly higher ORR and complete response rate at day 28, higher durable overall response at day 56 and longer failure-free survival in comparison with other regimens; inolimomab shows similar 1-year therapy success rate but superior long-term overall survial in comparison with anti-thymocyte globulin, other comparisons did not show significant differences in efficacy.

Conclusions: Adding MSCs to other second-line therapy regimens is associated with significantly improved ORR, ruxolitinib showed significantly better efficacy outcomes in comparison with other regimens in patients with SR aGVHD. Further well-designed RCTs and integrated studies are required to determine the optimal treatment.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

Keywords: acute graft-versus-host disease; mesenchymal stroma cells; meta-analysis; randomized controlled trials; ruxolitinib; second-line therapy; steroids-refractory.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The flow chart of study selection. CBM, China Biology Medicine; GVHD, graft-versus-host disease; RCT, randomized controlled trial.
Figure 2
Figure 2
Forest plot for meta-analysis including MSC-related trials. (A) Overall response rate at day 28. (B) Overall survival. MSC, mesenchymal stem cells.
Figure 3
Figure 3
Forest plot for subgroup analysis on ORR at day 28 according to (A) the grade of aGVHD and (B) the number of involved organs. aGVHD, acute graft-versus-host disease; MSC, mesenchymal stem cells.
See this image and copyright information in PMC

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