Abstract
Introduction: Steroid-refractory lower gastrointestinal acute graft-versus-host disease (SR-LGI-aGVHD) remains a life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab (VDZ), a gut-selective integrin antibody, has shown initial efficacy in treating LGI-aGVHD by specifically blocking the migration of T lymphocytes to the intestinal mucosa.
Methods: This study retrospectively analyzed 69 patients diagnosed with SR-LGI-aGVHD who received VDZ treatment at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 2022 to December 2024. The primary outcome was the overall response rate (ORR) of the lower gastrointestinal tract at day 28. Secondary outcomes included the one-year overall survival (OS) rate, steroid tapering, changes in immune markers, treatment safety, and prognostic factors. These indicators were calculated since VDZ treatment initiation.
Results：A total of 69 patients received a median of two 300-mg intravenous infusions of VDZ. 24.6% (17/69) received VDZ as second-line therapy, and 75.4% (52/69) as third-line therapy, and all received VDZ in combination with basiliximab. At baseline, 71.0% (49/69) patients presented with grade III/IV aGVHD and 62.3% (43/69) were classified as high-risk according to Minnesota criteria. The ORR at days 7, 14, 28, and 56 were 47.8% (33/69, CR 23.2%), 65.2% (45/69, CR 36.2%), 69.6% (48/69, CR 49.3%), and 71.2% (47/66, CR 63.8%), respectively. The median times to ORR and complete response (CR) were 9 (IQR 6-13) and 17 (IQR 931) days, respectively. A sustained CR was observed in 71.0% (49/69) of the patients.
Patients who achieved ORR by day 28 were younger (median age 36 vs. 41 years, P=0.028), had a higher proportion with ECOG performance status 0-1 (83.3% vs. 61.9%, P=0.067), and received a larger median CD34+ cell dose (4.23×10⁶ cells/kg vs. 3.42×10⁶ cells/kg, P=0.066). Additionally, they were more likely to be classified as standard risk (89.6% vs. 52.4%, P=0.001) and showed lower gastrointestinal MAGIC scores (grade 0-1: 89.6% vs. 57.1%, P=0.002) at onset . No significant differences were observed regarding the line of VDZ therapy (P=0.365), duration of treatment (P=0.232), aGVHD severity before VDZ treatment (P=0.235), or concomitant first-line ruxolitinib use (P=0.187).
The one-year incidence of cGVHD was 26.1% (18/69). The OS rate was 59.3% (95% CI, 48.5%-72.5%), with a significantly higher OS observed in the day-28 ORR group compared to all patients (77.4% vs. 59.3%, P=0.039) and day-28 non-ORR group (77.4% vs. 19.0%, P<0.0001). By day 28, 44.9% (31/69) of patients had successfully reduced steroid doses by at least 50% compared to VDZ treatment initiation (50 mg/d vs. 20 mg/d, P<0.001). Reduced levels of IL-12 (P=0.037) and TNF-α (P=0.074) were observed during the treatment. No severe VDZ-related adverse events were reported within the five half-lives period (approximately four months). Infections were the most common complications, including pneumonia (59.4%, 41/69), bloodstream infections (18.8%, 13/69), urinary tract infections (14.5%, 10/69), cytomegalovirus viremia (18.8%, 13/69), and Epstein-Barr virus viremia (15.9%, 11/69).
Conclusion VDZ demonstrated remarkable efficacy and safety as a second-line or third-line therapy for SR-LGI-aGVHD. This treatment approach achieved rapid and durable remission while improving survival rates and reducing steroid dependence.
