Researchers are reporting promising results from trials evaluating novel drug regimens aimed at reducing graft-versus-host disease (GVHD) following stem cell transplants. Two studies, one focusing on chronic GVHD (cGVHD) prevention and another on acute GVHD prevention, suggest new strategies to mitigate this life-threatening complication.
Novel Regimen Significantly Reduces Chronic GVHD
A team at Fred Hutch Cancer Center has tested a novel drug regimen for preventing moderate to severe cGVHD after stem cell transplants in blood cancer patients who received nonmyeloablative or reduced-intensity conditioning. The randomized Phase II study compared sirolimus, cyclosporine, and mycophenolate mofetil (SIR/CSP/MMF) against sirolimus, cyclosporine, and post-transplant cyclophosphamide (SIR/CSP/PTCy).
The results, presented at the Tandem Meetings in Honolulu, showed a significant reduction in cGVHD one year post-transplant in the PTCy group, with only 1% experiencing moderate to severe cGVHD compared to 28% in the control group. The estimated one-year cGVHD-free relapse-free survival was also higher in the PTCy group (76%) versus the control group (55%).
"PTCy has been a game changer for chronic GVHD, and our novel combination of drugs may work even better than previous combinations of drugs with PTCy," said Dr. Masumi Ueda Oshima, lead researcher for the study and associate professor in Fred Hutch’s Clinical Research Division.
The study enrolled 145 adults who underwent HLA-matched or HLA-mismatched transplants at Fred Hutch between November 2017 and May 2024. The SIR/CSP/PTCy regimen's success in mismatched transplants is particularly valuable for patients who struggle to find a full match, including those from underrepresented ethnic groups.
Itacitinib Shows Promise in Preventing Acute GVHD
In a separate development, a Phase I clinical trial at Washington University School of Medicine in St. Louis explored the use of itacitinib, an investigational JAK inhibitor, to prevent acute GVHD in patients undergoing half-matched stem cell transplants. The trial included 42 patients with various blood cancers, including acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome. All patients received itacitinib before and for 4-6 months after transplantation, alongside standard GVHD prevention.
Notably, none of the 42 patients developed severe (grade 3 or 4) acute GVHD within the first 180 days post-transplant. Historical data suggest that 10-15% of patients would typically experience severe acute GVHD with standard treatment. After one year, 89% of patients had no chronic GVHD, and overall survival was 80%.
"We have to be cautious about interpreting the results of a small study, but the rates of graft-versus-host disease were unexpectedly low," said senior author Dr. John F. DiPersio. "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."
Itacitinib functions by inhibiting specific enzymes that contribute to inflammation. While other JAK inhibitors are already FDA-approved for treating GVHD after it develops, this trial explores its potential as a preventative measure.
Future Directions
Both studies highlight the potential for novel drug regimens to improve outcomes for stem cell transplant recipients by reducing the incidence and severity of GVHD. Further research, including larger, randomized controlled trials, is needed to confirm these findings and optimize treatment strategies.
