Real World Experience on the Use of Vedolizumab for Treatment of Steroid Refractory Lower Gastrointestinal Acute Graft Versus Host Disease in Pediatric Allogeneic Stem Cell Transplant Recipients: A Multicenter Study

Introduction Data on the use of vedolizumab (a monoclonal antibody blocking α4β7 integrin) for treatment of lower gastrointestinal (LGI) acute graft versus host disease (aGVHD) post allogeneic hematopoietic stem cell transplantation (HCT) in pediatrics is restricted to case reports or single center studies with limited subject number and variable response rates. Objective We report the real-world outcomes on the safety and efficacy of vedolizumab for treatment of steroid refractory LGI aGVHD in children and young adults in a multi-center setting. Methods All patients who received vedolizumab for treatment of steroid refractory LGI aGVHD from 2017-2022 at 5 institutions were included. Descriptive statistics were used to analyze the data. Results Twenty-four patients with a median age 12.75 (range 0.25-25.17) years at HCT were included; majority were male (54%), with a malignant indication (69%) who received a myeloablative conditioning (67%). The median onset of aGVHD was 36.5 days (range 12-202 days) post-HCT with most patients (98%) having Grade III-IV aGVHD. Organ involvement at time of start of vedolizumab therapy were GI only (n=7), GI+ skin (n=11), GI + liver (n=1) and GI+ skin+ liver (n=5). A median of 4 doses (range 1-27) of vedolizumab were given starting at a median 115 days (32-330 days) post-HCT. Vedolizumab was given as 2nd line therapy (n=2) or as an adjunct 3-8th line agent (n=22). In patients surviving through day(D)+100 (n=23) post-vedolizumab therapy (Figure 1), D+28 intestinal responses showed an overall response rate (ORR) of 74% [complete response (CR): 6, very good partial response (VGPR): 6, partial response (PR):5] with 6 non-responders (NR). At D+100, the ORR was 69% (CR: 12, VGPR:4,) with 7 NR. Intestinal responses were sustained through D+180 (with 1 additional VGPR). Amongst D+28 responders (n=17), the mean baseline steroid dose decreased from 1.5 mg/kg (range 0-2.5 mg/kg) to 0.79 mg/kg (range 0-2.4mg/kg) at D+28 and 0.2 mg/kg (range 0-0.8 mg/kg) at D+100. Thirteen (54%) patients developed chronic GVHD (7 with GI or Liver involvement). No patient had infusion-related side effects. Post-vedolizumab therapy, twenty-three new infection events (10 bacterial,12 viral and 1 fungal) were observed in 15 (63%) patients. At a median follow up of 16 months (range 0.6-53), mortality was 37%, (n=9), with 11 of the fifteen surviving patients still receiving systemic immunosuppression (1 on vedolizumab). Conclusion Our data support the use of vedolizumab for ameliorating steroid refractory LGI aGVHD in children and young adults. However, its use in the real-world setting was mostly as an adjunct with multiple other lines of therapy, with an expected high incidence of infections due to use of extensive immune suppression in this cohort.