Successful treatment of steroid‐refractory gastrointestinal acute graft‐versus‐host disease with adjuvant vedolizumab therapy in a pediatric allogeneic stem cell transplant recipient

Abstract

LETTER TO THE EDITOR around D +224 she was diagnosed with pulmonary GVHD and therefore received photopheresis (biweekly) and ruxolitinb (5 mg twice daily). Ruxolitinb was discontinued due to lack of response and intolerance. She then received eight infusions of mesenchymal stromal cells (2 × 10 6 MSCs/kg) again with no response. On D +266 post-BMT, she commenced treatment intravenous vedolizumab (6 mg/kg: 200 mg) and received three doses on weeks 0, 2, and 6. She tolerated the infusions and experienced no side effects. She had a partial response on day 7 (stage one GI, grade II aGVHD) and complete response (grade 0 aGVHD) on day nine from the first and second dose of vedolizumab, respectively. Fecal calprotectin decreased from 1285 𝜇g/g (0-50 𝜇g/g) pre-vedolizumab to 295 𝜇g/g post-vedolizumab. The patient suffered no infectious complications. She is now 34 months post-BMT with no GI symptoms, gaining weight with a performance score of 90% and 99% donor chimerism in whole blood, CD3, and CD33 fractions. Her pulmonary GVHD responded to ibrutinib (started 23 months post-BMT). The clinical improvement seen in our single patient demonstrates that vedolizumab may be effective in children with SRaGVHD.Given the unmet need for novel therapies to treat SRaGVHD in children, 10 prospective pediatric studies using vedolizumab seems to be a reasonable option to pursue.

α4β7 Integrin expression and blockade in pediatric and young adult gastrointestinal graft‐versus‐host disease

“…In addition, vedolizumab has been used to treat steroid‐refractory acute GVHD in adults 18 . One case report has recently shown successful use of vedolizumab in one pediatric patient for the treatment of steroid‐refractory acute GVHD, further underscoring limited information about vedolizumab in children 19 . Additionally, no pediatric data exist regarding α4β7 integrin expression on T cells before or at GVHD diagnosis.…”

“…18 One case report has recently shown successful use of vedolizumab in one pediatric patient for the treatment of steroid-refractory acute GVHD, further underscoring limited information about vedolizumab in children. 19 Additionally, no pediatric data exist regarding α4β7 integrin expression on T cells before or at GVHD diagnosis. We therefore hypothesized that α4β7 integrin expression on memory T cells would be elevated in patients before and at acute GI GVHD compared to patients without acute GVHD, and that vedolizumab would be a promising agent for the management of acute GI GVHD in children.…”

Vedolizumab for pediatric patients with gastrointestinal acute graft‐versus‐host‐disease

“…Evidence of safety and efficacy of this modality for treating GI GVHD in children is scarce with only one case report and three case series recently published. [10][11][12][13] In this study, we present our experience in treating thirteen pediatric patients with vedolizumab for GI aGVHD. Acute GVHD International Consortium (MAGIC) staging criteria.…”

“…A similar response profile was reported in a few cases of pediatric patients published so far. [10][11][12][13] However, other case series that included adult patients with more severe disease, and with concurrent skin and liver involvement, showed less encouraging results. advantageous in these high-risk patients, where immune suppression may hamper the desirable graft-versus-leukemia effect.…”

“…Following recent reports of safe and efficacious treatment with vedolizumab for adult patients with aGVHD and reports of successful treatment in children with IBD, we started to treat selected pediatric patients, who presented with predominant GI manifestations of aGVHD, with vedolizumab. Evidence of safety and efficacy of this modality for treating GI GVHD in children is scarce with only one case report and three case series recently published 10–13 . In this study, we present our experience in treating thirteen pediatric patients with vedolizumab for GI aGVHD.…”