Clinical investigators are currently exploring ustekinumab, an IL-12 and IL-23 antagonist, for graft vs host disease (GVHD) prophylaxis in matched unrelated donor hematopoietic cell transplantation (HCT) recipients. A phase 2 clinical trial was launched to evaluate the potential of the agent for this therapeutic use.
The primary results from this trial were made available online for the 2026 Tandem Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and Center for International Blood and Marrow Transplant Research (CIBMTR) in Salt Lake City, Utah. On site at the conference, these results were presented by the trial’s first author, Joseph Pidala, MD, PhD, of the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida.
“We found confirmatory evidence of benefit in this multicenter, randomized, blinded study that manifested with improved GVHD-free survival, reduced acute GVHD, and reduced nonrelapse mortality,” Dr. Pidala said at the conclusion of the data presentation. However, he stressed that these benefits, found on subgroup analysis, were primarily seen in patients who had undergone myeloablative transplant conditioning. The study did not meet its primary end points of all-patient reduction of acute GVHD or improvement of GVHD-free survival (GFS).
The total trial cohort included 116 patients with hematologic malignancies aged 18 to 70 years from four US treatment centers. All patients had adequate vital organ functioning, had 8/8 matched unrelated donors, and had received peripheral blood stem cell grafts. Forty-eight percent of the patients had undergone myeloablative conditioning, and 52% had undergone reduced-intensity conditioning.
All patients were administered standard GVHD prophylaxis of tacrolimus plus methotrexate. Fifty-eight patients were randomized to receive ustekinumab in addition to this prophylaxis, and 58, to receive matched placebo. Ustekinumab was given as an IV induction dose 4 to 72 hours before the start of the patient’s HCT conditioning, then as subcutaneous injections at 50, 100, and 160 days after the transplant. The median patient ages were 56 years in the ustekinumab arm and 58 years in the placebo arm.
The trial’s primary end point was 6-month grade 2 to 4 acute GFS, and using the Cochran-Mantel-Haenszel test, the authors estimated a placebo-versus-ustekinumab odds ratio for end-point failure of 1.48 (one-sided P=0.15). However, subgroup analysis revealed a difference in 6-month GFS for myeloablative conditioning recipients, and secondary outcome results were favorable, with improved patient GFS at day 100 and reduced nonrelapse mortality.
Mark Forsberg, MD, of MD Anderson Cancer Center, during the question-and-answer session asked Dr. Pidala, based on the trial findings, what the place of ustekinumab may be relative to other agents being evaluated for GVHD prevention, such as abatacept. Dr. Pidala responded that the trial authors cannot say yet how ustekinumab compares against other potential new forms of GVHD prophylaxis and that the focus of their study was only to provide a comparison with placebo.
“In terms of where the future of this lies, we think, reviewing these data, that this really is most impressive in the myeloablative setting and that there is some kind of rationale as to why that may be, so I think future studies probably would focus on that domain,” Dr. Pidala explained.
