MPN-164: Overall Survival (OS) and Progression-Free Survival (PFS) in Patients Treated with Fedratinib as First-Line Myelofibrosis (MF) Therapy and after Prior Ruxolitinib (RUX): Results from the JAKARTA and JAKARTA2 Trials

Abstract

<h3>Introduction:</h3> The JAK2 inhibitor, fedratinib, significantly improved splenomegaly and myelofibrosis (MF) symptoms vs placebo as first-line treatment in the JAKARTA trial and after prior ruxolitinib in the JAKARTA2 trial. We determined PFS and OS with fedratinib 400 mg/day in these studies. <h3>Methods:</h3> Patients had intermediate- or high-risk MF. JAKARTA patients were randomized to fedratinib 400 mg/day, fedratinib 500 mg/day, or placebo. After six cycles (earlier if disease progression [PD]), placebo-randomized patients could crossover to fedratinib. In JAKARTA2, all patients with MF resistant/intolerant to RUX initially received fedratinib 400 mg/day. PFS was time from randomization to PD/death. PFS/OS in the placebo arm of JAKARTA included time after crossover to fedratinib. Both trials were terminated early due to a clinical hold in 2013; ongoing patients were censored for PFS/OS. <h3>Results:</h3> In JAKARTA, 96 patients were randomized to fedratinib 400 mg and 96 to placebo; 71 placebo-randomized patients (74%) crossed over to fedratinib. At study termination, survival follow-up halted for 74 fedratinib-randomized pts (77%) and 65 placebo-randomized pts (68%). Median (m) PFS was prolonged with fedratinib <i>vs</i> placebo: 23.2 <i>vs</i> 17.5 months, respectively (HR 0.42 [95%CI 0.23–0.76]; P=0.004); 1-year PFS rates were 83% <i>vs</i> 67%. mOS was not reached (NR) in either arm (HR 0.57 [0.30–1.10]; P=0.094); 1-year survival was 92% with fedratinib and 86% with placebo. Of 97 patients enrolled in JAKARTA2, 79 (81%) were censored for survival at study termination. mPFS was 13.3 months (95%CI 8.4–17.1), and mOS was NR (17.1 months-NR), with a 1-year PFS of 59% and 1-year survival rate of 84%. <h3>Conclusions:</h3> Fedratinib 400 mg/day significantly improved PFS <i>vs</i> placebo as first-line MF treatment. Separation of PFS/OS curves between fedratinib and placebo in JAKARTA, despite substantial fedratinib crossover for placebo-randomized patients, suggests early fedratinib treatment is better. In JAKARTA2, mPFS, mOS, and 1-year survival compare favorably with findings in similar patients post-RUX (6.0 months, 11.1 months, and 47%, respectively; Mascarenhas 2020). The FREEDOM and FREEDOM2 trials of fedratinib are ongoing. Adapted from CN Harrison, et al., Overall and progression-free survival in patients treated with fedratinib as first-line myelofibrosis (MF) therapy and after prior ruxolitinib (RUX): results from the JAKARTA and JAKARTA2 trials, HemaSphere, 2021; Abstract S203.