A phase 1 trial investigated the safety and tolerability of maintenance therapy with the JAK2 inhibitor fedratinib (Inrebic) following allogeneic hematopoietic cell transplant (HCT) for myeloproliferative neoplasms (MPNs) and myelodysplastic syndrome/MPN overlap syndromes.
While HCT offers potential cure for MPNs, posttransplant relapse remains a significant challenge. Fedratinib, effective 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.
“Usually with fedratinib, the main toxicities are cytopenia, so low blood counts. We also see a fair amount of [gastrointestinal (GI)] toxicity, nausea, vomiting, or diarrhea,” said Hany Elmariah, MD, associate member at the Moffitt Cancer Center in the Department of Bone Marrow Transplant and Cellular Immunotherapy, in an interview with Targeted OncologyTM.
The study enrolled patients post-HCT who received fedratinib between days +60 and +100 for up to 1 year. The trial 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%.