TIDRAKIZUMAB FOR THE PROPHYLAXIS OF GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

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. Fifty patients were enrolled between March 2020 and June 2023 with a median age of 56 (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 five doses which was well tolerated. The cumulative incidences of grades II-IV and III-IV acute graft versus host disease were 14% (95% 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 twelve months. The one-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 that the half-life of tildrakizumab approximated 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. NCT04112810.