Targeted GvHD prophylaxis: Vedolizumab in the GvHD prevention regime with post-transplant cyclophophospamide, abatacept, calceneurin inhibitors in adults with hematologic disease: Result prospective study

Abstract Introduction Acute graft-versus-host disease (aGvHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT), with gastrointestinal (GI) involvement associated with the highest mortality. Selective blockade of α4β7-integrin by the monoclonal antibody vedolizumab is a promising targeted prophylaxis strategy. This study evaluated the efficacy of a four-drug regimen combining vedolizumab (300 mg IV on days -1, +14, +28), tacrolimus(0.03 mg/kg from day -1 to +120), abatacept (10 mg/kg IV on days -1, +5, +14, +28, +60, +90), and post-transplant cyclophosphamide (PTCy) (50 mg/kg on days +3, +4 in 60.7% of patients). Materials and Methods A prospective single-center study included 84 patients (median age 49.5 years [19–66]; 61.9% male) with hematologic malignancies: Acute Myeloid Leukemia (61.9%), Acute Lymphoblastic Leukemia (14.3%), Myelodysplastic Syndrome (6%), Аplastic anemia (4.8%), and others. All underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from related or unrelated donors (haploidentical: 54.8%, HLA-matched: 39.3%). Vedolizumab in the GvHD prevention regime with PTCy, abatacept, calceneurin inhibitors in adults with hematologic disease. Primary endpoints Cumulative incidence of aGvHD II-IV (Glucksberg criteria) by day +100, The cumulative incidence of gut aGVHD grade II-IV, engraftment, and overall survival (OS). Results Engraftment was achieved in 95.2% (median time: 12 days [9–21]). Grade II–IV aGvHD: 14.28% (n=12; 95% 23.62-7.61). Grade III–IV aGvHD: 5.95% (95% 13.35-1.96) (3 patients - grade III, 2 – grade IV). The cumulative incidence of gut aGVHD grade II-IV was 3.57% (n=3; 95% CI 1.3–98.1), with no grade IV cases. Early transplant-related mortality: 7.14%. Median OS: 383 days. Conclusion The combination of vedolizumab with standard GvHD prophylaxis demonstrated: High efficacy in preventing severe GI aGvHD (≤grade III: 3.57%; no grade IV). Favorable safety without compromising engraftment. Warranting further validation in randomized trials.