Elmariah on Maintenance Therapy Posttransplant for Myelofibrosis Relapse and GVHD Prevention
Hany Elmariah, MD, discusses incorporating fedratinib as maintenance therapy in the posttransplant setting to prevent relapse of MPNs and graft-vs-host disease.
A phase 1 trial evaluated the safety and tolerability of maintenance therapy with the JAK2 inhibitor fedratinib (Inrebic) after allogeneic hematopoietic cell transplant (HCT) for the treatment of myelofibrosis and myeloproliferative neoplasms (MPNs).
While HCT is potentially curative for MPNs, posttransplant relapse remains a significant challenge.
"While transplant can be curative, the cure rate, depending on which study you look at, is somewhere in the 40% to 60% range. And then the reason for patients to ultimately not be cured by the transplant is largely driven by the risk of relapse, which is where the cancer comes back after the transplant. And for those who don't relapse, there's also a risk of toxicity, such as graft-vs-host disease, which is where the transplant attacks the patient's own body," said Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the Department of Bone Marrow Transplant and Cellular Immunotherapy.
Fedratinib, effective in the pretransplant setting in myelofibrosis, with a favorable safety profile and oral administration, presents a rational strategy to reduce relapse and potentially prevent graft-vs-host disease (GVHD) while preserving the graft-vs-tumor (GVT) effect.
"So in the case of myelofibrosis, one appealing group of drugs for that are what are called JAK2 inhibitors. So the JAK2 inhibitor that we chose specifically is called fedratinib, which is FDA approved for the treatment of myelofibrosis in patients before transplant. And the goal here was to see fedratinib could reduce the risk of posttransplant relapse in patients myelofibrosis. Also, this class of drugs called JAK2 inhibitors is also proven effective for the treatment of graft-vs-host disease. And so in this particular study, this maintenance strategy, hopefully, our goal was to see if it could kind of kill 2 birds with 1 stone, both reduce relapse because it's directed against myelofibrosis, and also prevent graft-vs-host disease by blocking this JAK pathway that we know now is implicated in the pathophysiology of graft-vs-host," Elmariah explained.
The study enrolled patients post-HCT who were administered fedratinib between days +60 and +100 for up to 1 year. The study utilized a 3+3 design to determine the maximum tolerated dose (MTD). Eleven patients were evaluable for dose-limiting toxicities (DLTs). The MTD was identified as 400 mg daily. While no DLTs occurred within the 30-day window, 4 patients withdrew due to non-DLT adverse events. Notably, only 1 patient developed severe chronic GVHD. The median progression-free survival was 12.4 months, and the 1-year overall survival was 100%.
Fedratinib at 400 mg daily appeared to be safe as maintenance after allogeneic HCT. A phase 2 expansion cohort is currently enrolling to further evaluate the long-term safety and efficacy of this maintenance strategy in preventing relapse and GVHD in MPN patients post-HCT.
