Budesonide, Added to PTCy-Based Regimen, for Prevention of Acute GI GVHD After Allogeneic Stem Cell Transplantation

Oral budesonide exerts local effects with negligible systemic glucocorticoid activity, due to rapid first-pass metabolism, therefore, could potentially be efficacious in preventing gastrointestinal (GI) acute GVHD (aGVHD). We explored the use of budesonide, added to posttransplant cyclophosphamide (PTCy), tacrolimus, and mycophenolate mofetil, for prevention of GI aGVHD after allogeneic hematopoietic stem cell transplantation (AHSCT) in a prospective observational study and treated 80 patients with a median age of 53 years (range 19–74). Results were compared with a publicly available CIBMTR dataset of 646 patients who received PTCy-based GVHD prophylaxis (CIBMTR Study # GV17-02) (control). Cumulative incidence (CI) of 3-month grade 2–4 and grade 3–4 aGVHD in the budesonide and control groups were 3.8% vs. 34.4% (p < 0.001) and 1.3% vs. 9.8% (p = 0.029), respectively. One-year GRFS (70.5% vs. 31.5%, p < 0.001), PFS (73.4% vs. 52.8%, p = 0.003), and OS (80.1% vs. 64.2%, p = 0.038) were significantly higher in the budesonide group compared with control group. Propensity score-adjusted analyses showed that the addition of budesonide significantly decreased risk of aGVHD grade 2–4 (HR 0.29, p < 0.001), grade 3–4 (HR 0.12, p = 0.045), and cGVHD (HR 0.22, p < 0.001), which resulted in better GRFS (HR 0.38, p < 0.001), PFS (HR 0.58, p = 0.012), and OS (HR 0.72, p = 0.044). Similar results were found when using propensity score-matched analysis restricted to recipients of haploidentical transplantation. In conclusion, addition of budesonide to PTCy-based GVHD prophylaxis is safe and effective in preventing severe acute GI GVHD with significantly improved GRFS. These results could facilitate transition to peripheral blood grafts for all allogeneic transplant recipients.