Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Blood Adv 2026 Apr 28;10(8):2698-2710
Date
02/03/2026Pubmed ID
41632629Pubmed Central ID
PMC13101680DOI
10.1182/bloodadvances.2025019065Scopus ID
2-s2.0-105035803096 (requires institutional sign-in at Scopus site)Abstract
We conducted a phase 1/2 study in which patients undergoing allogeneic hematopoietic stem cell transplantation received tildrakizumab in addition to standard immune suppression with tacrolimus and methotrexate for graft-versus-host disease (GVHD) prophylaxis. A total of 50 patients were enrolled between March 2020 and June 2023 with a median age of 56 years (range, 19-64). All patients received myeloablative busulfan-based conditioning and were transplanted with HLA-matched related or unrelated peripheral blood stem cell grafts. Patients were treated with tildrakizumab on an extended subcutaneous administration schedule for 5 doses, which was well tolerated. The cumulative incidences of grades 2 to 4 and 3 to 4 acute GVHD were 14% (95% confidence interval [CI], 7-28) and 4% (95% CI, 1-16) at day 100, respectively. The incidence of chronic GVHD requiring systemic immune suppression was 52.7% (95% CI, 40.4-68.9) at 12 months. The 1-year probabilities of overall, disease-free, and GVHD-free relapse-free survival were 80% (95% CI, 70-92), 78% (95% CI, 67-90), and 19.3% (90% CI, 11.8-31.4), respectively. Pharmacokinetic analysis revealed the half-life of tildrakizumab at ∼28 days without formation of detectable anti-tildrakizumab-neutralizing antibodies. Comparative examination of fecal microbial composition in tildrakizumab and a similarly transplanted cohort treated with tocilizumab prophylaxis demonstrated that both cytokine blockade strategies had a low frequency of enterococcal dominance. We conclude that tildrakizumab resulted in a low incidence of acute GVHD and attenuation of microbiome dominance with potentially pathogenic organisms but did not mitigate the emergence of chronic GVHD as administered on this dosing schedule. This trial was registered at www.clinicaltrials.gov as #NCT04112810.
Author List
Runaas L, Fank S, Palen K, Szabo A, Rein LE, Ying G, Salzman N, Samanas L, Abedin S, Chhabra S, Hamadani M, Longo W, Shah NN, Haber J, Gradissimo A, Waters N, Peled JU, Johnson B, Kearl T, Drobyski WRAuthors
Sameem Abedin MD Associate Professor in the Medicine department at Medical College of WisconsinWilliam R. Drobyski MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi Hamadani MBBS Professor in the Medicine department at Medical College of Wisconsin
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Tyce J. Kearl PhD, MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Walter L. Longo MD Professor in the Medicine department at Medical College of Wisconsin
Lisa E. Rein MSc Biostatistician III in the Data Science Institute department at Medical College of Wisconsin
Nita H. Salzman PhD, MD Center Director in the Pediatrics department at Medical College of Wisconsin
Nirav N. Shah MD Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultAntibodies, Monoclonal, Humanized
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Male
Middle Aged
Transplantation Conditioning
Transplantation, Homologous
Young Adult
