Adding a new drug to standard care for stem cell transplant recipients may reduce graft-versus-host disease (GvHD), 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 itacitinib and experienced lower-than-expected rates of GvHD. 

“We have to be cautious about interpreting the results of a small study, but the rates of GvHD were unexpectedly low,” said senior author John DiPersio, the Virginia E & Sam J Golman Endowed Professor of Medicine. “We saw no severe GvHD, and the rates of relapse were lower than expected in these high-risk patients. Low GvHD rates and low relapse resulted in very encouraging survival for the patients in this study. These early results are compelling, and we hope to conduct a bigger randomised controlled clinical trial to be able to evaluate efficacy.” 

The Phase I trial involved patients who received a ‘half-match’ stem cell transplant, in which half of the key proteins of a patient’s immune system matched those of the donor’s stem cells. These have become more common over the past decade as treatments to reduce GvHD have improved. 

JAK inhibitors as a prevention strategy 

The trial included 42 patients, most of whom had been diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia or myelodysplastic syndrome, among other, rarer blood cancers. All patients in the study received itacitinib before transplantation and for four to six months after transplant, in addition to standard care for prevention of GvHD. 

None of the 42 patients developed severe (grade 3 or 4) GvHD in the first 180 days after the transplant. Historical data suggest 10-15% of patients would experience severe GvHD with standard treatment. 

After one year, 89% of patients had no chronic GvHD and just two patients developed moderate GvHD. Overall survival at one year was 80%. 

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. 

“Some other JAK inhibitors are already approved by the Food and Drug Administration to treat acute and chronic GvHD after it develops,” said first author Ramzi Abboud, Assistant Professor of Medicine in the Division of Oncology at WashU Medicine. “We are interested in investigating these drugs as a possible way to prevent GvHD by giving them before the transplant. We suspect that JAK inhibitors will have a place in prevention of this life-threatening side effect of stem cell transplants. This study is encouraging, and we expect to know more about how best to use these prevention strategies in the coming years.”

Diana Spencer, Senior Digital Content Editor, DDW