Photo Credit: Nemes Laszlo

The following is a summary of “Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib (FREEDOM2): results from a multicentre, open label, randomized, controlled, phase 3 trial,” published in the October 2024 issue of Hematology by Harrison et al.   

Many patients with myelofibrosis struggle with ruxolitinib intolerance or experience a relapse, leading to low survival rates after stopping the treatment.   

Researchers conducted a retrospective study assessing how well fedratinib works compared to the best available therapy for these patients.   

They conducted the FREEDOM2 trial across 86 clinics in 16 countries, involving adults with intermediate-2 or high-risk myelofibrosis who were intolerant to ruxolitinib. Participants were randomly assigned to receive either fedratinib (4 x 100 mg per day orally) or the best available therapy (BAT), with their progress monitored for spleen volume reduction (SVR) of at least 35% (SVR35) at the end of cycle 6 in intention-to-treat population.   

The results showed that between September 2019 and June 2022, 316 patients were screened, with 201 assigned to treatment (134 to fedratinib and 67 to BAT, including 52 on ruxolitinib. At the data cutoff, median follow-up was 64.5 weeks (IQR: 37.9-104.9). The SVR35 was achieved by 36% of patients (n=48) treated with fedratinib compared to 6% of 67 patients treated in the BAT group (30% difference; 95% CI 20–39; P<0·0001). Grade 3 or higher treatment-related adverse events were seen in 40% of patients (n=53) treated with fedratinib and 12 % (n=8) in the BAT group, mainly anemia (fedratinib 12 [9%] of 134, BAT 6 [9%] of 67) and thrombocytopenia (fedratinib 16 [12%] of 134; BAT 2 [3%] of 67). Only 1 patient died from suspected acute kidney injury, whereas no treatment related deaths in the BAT group were recorded. Gastrointestinal issues were more common in the fedratinib group but mostly mild. A total of 28 (21%) patients in the fedratinib group and 3 (4%) in the BAT group had thiamine levels below the lower limit of normal per central laboratory assessment.   

Investigators concluded that fedratinib offers a viable second-line Janus kinase inhibitor option for reducing spleen size in patients with myelofibrosis who experience failure or intolerance to ruxolitinib.   

Source: sciencedirect.com/science/article/abs/pii/S2352302624002126