Stem cell transplantation is a method used to treat various forms of blood cancers, but it comes with the danger of a serious complication known as graft-versus-host disease (GvHD). Recent findings from a clinical trial indicate that incorporating an experimental drug named itacitinib into the standard care regimen for ‘half-matched’ stem cell transplantation may help lower the incidence of GvHD, which occurs when the donor’s stem cells attack the recipient’s healthy tissues.
A recent early-stage clinical trial conducted at Washington University School of Medicine in St. Louis suggests that introducing a new medication could lessen a potentially fatal side effect for individuals undergoing stem cell transplants. The study found that patients treated for various blood cancers tolerated the investigational drug, itacitinib, and exhibited lower-than-anticipated rates of graft-versus-host disease (GvHD), where the donor’s stem cells target the recipient’s healthy tissues.
The findings have been published in the journal Blood.
“While we must be careful when interpreting the results of a small study, the observed rates of graft-versus-host disease were surprisingly low,” noted senior author John F. DiPersio, MD, PhD, who holds the Virginia E. & Sam J. Golman Endowed Professor of Medicine title. “We found no cases of severe GvHD, and the relapse rates were also lower than expected in these high-risk patients. The combination of low GvHD rates and recurrences resulted in very promising survival outcomes for the participants in this study. These initial findings are compelling, and we hope to progress toward a larger randomized controlled trial to further assess efficacy.”
Conducted at Siteman Cancer Center, affiliated with Barnes-Jewish Hospital and WashU Medicine, this Phase I trial involved patients who underwent a specialized type of stem cell transplant known as a “half-match,” where half of the essential immune system proteins matched between the recipient and the donor. Stem cell transplantation is a standard treatment option for various blood cancers, such as leukemia and lymphoma.
While a fully matched donor is generally preferred to minimize the risk of graft-versus-host disease, finding such donors can be challenging and may delay treatment initiation. Patients’ parents or children are always half-matched, with siblings being half-matched half of the time, making these donors more accessible for most individuals. Over the last decade, half-match stem cell transplants have become increasingly common due to improvements in treatments aimed at reducing graft-versus-host disease, making these procedures safer.
“The rise in half-matched transplants in recent years emphasizes the necessity of enhancing the safety and efficacy of this procedure, which holds promise for a large patient population,” DiPersio stated.
The trial evaluated 42 patients, primarily those diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome, among some rarer blood cancer types. Each participant received itacitinib both prior to and for 4-6 months following the transplant, alongside standard care intended to prevent graft-versus-host disease.
Notably, none of the 42 participants developed severe (grade 3 or 4) graft-versus-host disease within the first 180 days following the transplant. This study lacked a control group, focusing instead on safety rather than treatment efficacy. Nonetheless, historical data indicates that around 10 – 15% of patients typically experience severe graft-versus-host disease with standard care, implying that statistically, four to six individuals in this trial might have developed severe cases.
After one year, 89% of the participants showed no signs of chronic graft-versus-host disease. Two participants did develop moderate or severe chronic GvHD at that time, and they were given additional treatments. The overall survival rate after one year stood at 80%, which is on the higher end of the usual survival range for such patients, typically between 60 – 80% at one year.
The investigational medication itacitinib is among several JAK inhibitors being studied for their potential to prevent graft-versus-host disease when administered prior to a stem cell transplant, offering a novel therapeutic approach. JAK inhibitors function by inhibiting the action of certain enzymes that contribute to inflammation.
“Some other JAK inhibitors have already received approval from the Food and Drug Administration for treating acute and chronic graft-versus-host disease once it occurs,” said first author Ramzi Abboud, MD, an assistant professor of medicine in the Division of Oncology at WashU Medicine. “We are keen to explore these drugs for their potential to prevent graft-versus-host disease by administering them before the transplant. We believe that JAK inhibitors may play an important role in preventing this severe complication of stem cell transplants. Our team and others are actively assessing these medications in clinical trials utilizing various strategies. This study shows promise, and we anticipate gaining further insights into the most effective use of these preventive measures in the coming years.”
