By Patrick Daly – Last Updated: January 17, 2024
Treatment with fedratinib, a Janus kinase inhibitor (JAKi), induced superior spleen volume reduction (SVR) and symptom response rates compared with best available therapy in patients with myelofibrosis (MF) who previously received ruxolitinib, according to data from the open-label phase III FREEDOM2 study, presented at the 65th American Society of Hematology Annual Meeting & Exposition.
“Most patients on best available therapy received ruxolitinib, highlighting a need for an alternative JAKi,” stated lead author of the study, Claire Harrison, MD, FRCP, from Guy’s and St. Thomas’ NHS Foundation Trust in London, England.
The FREEDOM2 trial enrolled patients aged 18 years or older with primary, post-polycythemia vera, or post-essential thrombocythemia MF with splenomegaly who were intolerant or refractory to, or relapsed after ruxolitinib. The primary endpoint was SVR ≥35% (SVR35) at the end of the sixth 28-day cycle.
Fedratinib for Myelofibrosis Treatment Superior to Ruxolitinib
In total, 201 patients were randomized to fedratinib (n=134) or best available therapy (n=67). The cohort had a median age of 70 (interquartile range, 64-74), 52.2% were male, 54.7% had primary MF, and 76.1% had a Dynamic International Prognostic Scoring System risk score of intermediate-2.
Overall, 70.1% of patients in the best available therapy arm received ruxolitinib, 10.4% received hydroxyurea, and 7.5% received ruxolitinib plus hydroxyurea. Additionally, 46 (68.7%) patients in the best available therapy arm crossed over to fedratinib after either disease progression or the sixth cycle response assessment.
With a median follow-up of 15 months at the data cutoff, researchers reported the fedratinib group had a significantly higher SVR35 rate of 35.8% at the end of cycle six compared with best available therapy at 6.0% (P<.0001). Fedratinib also yielded superior SVR ≥25% at the cycle six assessment and superior SVR35 at any point during treatment. The rate of symptom response at the end of cycle six was 34.1% with fedratinib versus 16.9% with best available therapy (P=.0033).
In short, “fedratinib demonstrated superior SVR and symptom response rates compared with [best available therapy]” in patients with MF and prior ruxolitinib treatment, concluded Dr. Harrison and colleagues.
Reference
Harrison CN, Mesa RA, Talpaz M, et al. Efficacy and safety of fedratinib in patients with myelofibrosis previously treated with ruxolitinib: results from the phase 3 randomized FREEDOM2 study. Abstract #3204. Presented at the 65th ASH Annual Meeting & Exposition; December 9-12, 2023; San Diego, California.