Multinational phase 3 trial of fedratinib for myelofibrosis in patients previously treated with ruxolitinib

Most patients with myelofibrosis develop ruxolitinib intolerance or disease that is relapsed or refractory, and survival rates after ruxolitinib discontinuation are poor. The multinational phase 3 FREEDOM2 trial (86 clinics in 16 countries) evaluated fedratinib versus best available therapy (BAT) in patients with myelofibrosis previously treated with ruxolitinib. Primary endpoint was proportion of patients reaching spleen volume reduction of at least 35% (SVR35) at end of cycle 6. This endpoint was reached by 36% of patients in the fedratinib group versus 6% of patients in the BAT group. Grade 3 or higher treatment-related adverse events during the first 6 cycles were reported for 40% of patients in the fedratinib group and 12% of patients in the BAT group. One patient in the fedratinib group died from acute kidney injury suspected to be related to the study drug. Gastrointestinal adverse events occurred more frequently in the fedratinib group compared with the BAT group but were mostly grade 1 or 2 in severity and more frequent inearly cycles, and were less frequent than in prior clinical trials. The authors conclude that findings from FREEDOM2 support fedratinib as a second-line option to reduce spleen size after discontinuation of ruxolitinib in patients with myelofibrosis.