Tildrakizumab for the prophylaxis of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

abstractWe 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.