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

Abstract

ObjectiveSteroids-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.MethodsLiterature 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.ResultsEight 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.ConclusionsAdding 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 registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022342487.

Drug exporter expression correlates with group 3 innate lymphoid cell resistance to immunosuppressive agents

“…In patients with acute GvHD where tissue damage is dominant, prednisolone may actually aggravate disease by suppressing ILC3 mediated IL-22 production. It should be noted that patients with steroid-refractory acute GvHD often benefit from ruxolitinib (33), perhaps via enhanced IL-22 production by ILC3.…”

Editorial: 50 years of BMT: risk stratification, donor matching and stem cell collection for transplantation

“…The advent of new tools and protocols to detect and treat fungal infections improved control of infections by Aspergillus , mucormycosis, and Candida . The early diagnosis and prevention of Cytomegalovirus were considerable advances, as well as treatment of reactivation/persistence ( 26 ). New drugs and procedures have emerged to prevent and treat major transplantation complications such as mucositis, hepatic veno-occlusive disease, and GVHD.…”