Clinical Trial Shows Drug Reduces Risk of Graft-Versus-Host Disease in Stem Cell Transplants - Video

Adding a new drug to standard care for stem cell transplant recipients may reduce a life-threatening side effect, according to an early-stage clinical trial conducted at Washington University School of Medicine in St. Louis. The trial showed that patients being treated for various blood cancers tolerated the investigational drug — called itacitinib —and experienced lower-than-expected rates of graft-versus-host disease (

GvHD), in which the donor’s stem cells attack the patient’s healthy tissues. The study is online in the journal Blood.

The Phase I trial involved patients who received a particular stem cell transplant — called a “half-match” — in which half of the key proteins of a patient’s immune system matched those of the donor’s stem cells.

The trial included 42 patients, most of whom had been diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia or myelodysplastic syndrome, among other, rarer blood cancers. All patients in the study received itacitinib before transplantation and for 4-6 months after transplant, in addition to standard care for prevention of graft-versus-host disease.

None of the 42 patients developed severe (grade 3 or 4) graft-versus-host disease in the first 180 days after the transplant. There was no control group in this study, which was designed to assess the safety but not the efficacy of the treatment. Even so, historical data suggest 10 – 15% of patients would experience severe graft-versus-host disease with standard treatment, according to the investigators. Therefore, statistically, four to six patients in this sample size would be expected to develop severe forms of the disease.

After one year, 89% of patients had no chronic graft-versus-host disease. Two patients developed moderate or severe chronic graft-versus-host disease at that same timepoint, and they were treated with additional therapies. Overall survival at one year was 80%. This is on the high end of what is typically seen in such patients, whose survival can range from 60 – 80% at one year.

The investigational drug itacitinib is one of several JAK inhibitors under investigation for their potential to prevent graft-versus-host disease when given before a stem cell transplant, which would be a new use for this therapy. JAK inhibitors work by blocking the activity of specific enzymes that contributes to inflammation.

Reference: Ramzi Abboud, Mark A. Schroeder, Michael P Rettig, Reyka G Jayasinghe, Feng Gao, Jeremy Eisele, Leah Gehrs, Julie K. Ritchey, Jaebok Choi, Camille N Abboud, Iskra Pusic, Meagan A Jacoby, Peter Westervelt, Matthew Christopher, Amanda F. Cashen, Armin Ghobadi, Keith Stockerl-Goldstein, Geoffrey L Uy, John F. DiPersio; Itacitinib for Prevention of Graft-Versus-Host Disease and Cytokine Release Syndrome in Haploidentical Transplantation. Blood 2024; blood.2024026497. doi: https://doi.org/10.1182/blood.2024026497