A new phase 2 prospective study has demonstrated significant promise for ruxolitinib in preventing graft-versus-host disease (GVHD) in myelofibrosis patients undergoing hematopoietic cell transplantation (HCT), marking a potential advancement in transplant medicine.
The study (NCT04384692), conducted at Fred Hutchinson Cancer Center, revealed that adding ruxolitinib to standard GVHD prophylaxis substantially reduced both acute and chronic GVHD incidence while maintaining high survival rates. Grade II to IV acute GVHD occurred in only 32% of patients receiving peri-transplant ruxolitinib, compared to 71% in a previous study using pre-transplant ruxolitinib.
Improved Patient Outcomes
The trial demonstrated remarkable survival statistics, with overall survival rates reaching 100% at one year and 87% at two years. Chronic GVHD rates at one year were notably low at 12%, compared to 25% in the pre-transplant ruxolitinib group.
"The incidence of acute and chronic GVHD was markedly reduced without the expense of non-relapse mortality, relapse, or survival. It doesn't appear that infections or transfusion needs were increased," stated Dr. Rachel B. Salit, associate professor at Fred Hutchinson Cancer Center.
Study Design and Patient Characteristics
The trial enrolled 25 patients with myelofibrosis, with a median age of 66 years. Patients received ruxolitinib at least 8 weeks before HCT, with careful dose management throughout the transplant process. The treatment protocol included:
- Ruxolitinib tapering to 5 mg twice daily by day 4 pre-HCT
- Standard tacrolimus and methotrexate GVHD prophylaxis
- Continued ruxolitinib administration through cell infusion until 2 months after tacrolimus discontinuation
The patient cohort comprised 60% primary myelofibrosis cases and 40% secondary myelofibrosis, with 68% being JAK2 positive. The majority (76%) received transplants from unrelated donors, with reduced-intensity conditioning used in 68% of cases.
Safety and Efficacy Metrics
The study reported encouraging safety data:
- No primary graft failures
- Median time to engraftment of 20 days
- Only 4% relapse rate at 1 year
- 12% non-relapse mortality at 1 year
While infectious adverse events were observed, with 20 patients experiencing grade 3 events and 4 patients having grade 4 events, these rates were considered manageable within the context of transplant procedures.
Future Directions
Dr. Salit indicated that ongoing research is focusing on GVHD biomarkers, STAT signaling, and disease modification with post-transplant ruxolitinib. Future clinical trials will aim to optimize dose timing and tapering strategies for peri-transplant ruxolitinib administration.
This research represents a significant step forward in transplant medicine for myelofibrosis patients, offering a promising approach to reducing GVHD risk while maintaining therapeutic efficacy.
