Budesonide Use for Grade 2 Gastrointestinal Graft-Versus-Host Disease after Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis

Introduction Allogeneic hematopoietic stem cell transplant (HCT) is a potentially curative treatment in patients with high-risk hematological malignancies. The introduction of post-transplant cyclophosphamide (PTCy) has allowed the ability to reduce immunological complications and increase the pool of suitable donors, increasing access to many HLA-disparate patients in the HLA mismatched setting with acceptable graft-versus-host disease (GVHD) rates, and even challenged the conventional use of calcineurin and methotrexate based GVHD prophylaxis strategies in the HLA-identical donor setting for HCT. In patients receiving PTCy who develop grade 2 isolated gastrointestinal (GI) GVHD, treatment with nonabsorbable steroids, such as budesonide, without systemic treatment may be feasible, though this has not been explored yet in the literature. Here we analyze response to budesonide monotherapy for isolated grade 2 acute upper GI GVHD in this patient population. Objective(s) The primary objective of this study is to analyze response to budesonide monotherapy for isolated grade 2 acute GI GVHD in patients receiving PTCy for GVHD prophylaxis regimen following allogeneic HCT. Methods This is a single-center, retrospective, case series of allogeneic HCT adult patients (>18 years) who received PTCy-based GVHD prophylaxis between April 2015 to October 2021. Patients who developed isolated grade 2 GI GVHD initially treated with budesonide monotherapy within the first 100 days of transplant were included for analysis. The primary endpoints are the overall response to budesonide at day 30 and 90 and incidence of progression to systemic therapy. Secondary endpoints included time to systemic therapy. Results Between April 2015 to October 2021, 298 patients were transplanted with a PTCy based GVHD prophylaxis regimen. Of this population, 75 (25.1%) developed grade 2 isolated GI GVHD and 66 (88%) of patients with grade 2 isolated GI GVHD started on budesonide monotherapy (table). Overall response to budesonide at day 30 and 90 was 75.8% (n=50) and 66.2% (n=43), respectively. In patients who received budesonide monotherapy, 43 (66.2%) responded without initiation of systemic therapy. The cumulative incidence of systemic therapy is depicted in figure. The median time to initiation of systemic therapy was 35.5 days (range 1-289) from start of budesonide. Conclusion In patients who underwent HCT with PTCy based GVHD prophylaxis with isolated grade 2 GI GVHD budesonide monotherapy resulted in good responses without the addition of systemic therapy, sparing the majority of patients toxicities associated with systemic treatment.