Outcomes of Fedratinib in routine Treatment of ruxolitinib-resistant or refractory patients with Primary and post-polycythemia vera or essential thrombocythemia Myelofibrosis: A nationalwide retrospective study.

INTRODUCTION In recent years, fedratinib, a selective JAK2 inhibitor, has emerged as a potential therapeutic option for patients who have failed or are intolerant to ruxolitinib. Despite the promising results observed in clinical studies, real-world evidence from the United States and Europe suggests that the efficacy of fedratinib may be less conclusive. We report the characteristics, treatment patterns, and clinical outcomes of patients with myelofibrosis (MF) treated with fedratinib following ruxolitinib failure in Israel's clinical practice. METHODS This retrospective patient chart review included adults with a physician-reported diagnosis of MF, who initiated fedratinib after discontinuing ruxolitinib. Descriptive analyses characterized patient characteristics, clinical outcomes, and treatment patterns from MF diagnosis through ruxolitinib and fedratinib treatment. RESULTS We extracted data for 16 eligible patients. Approximately 62.5 % of the patients were female, and the median age was 77 (range, 63-85) years. The median duration of ruxolitinib therapy was 17 months (range 3-84 ) months. Before the initiation of fedratinib, the median spleen size by palpation was 15.5cm below the costal margin (range 4-22cm). After three months the median spleen size was 13cm below the costal margin (range 2-21 cm). Only two patients showed minimal improvement after six months, while three patients progressed, and two patients showed no change in the spleen size. The spleen response did not improve after 12 months of treatment. At this point, the median spleen size was 19 cm below the costal margin (range 2-30 cm). Regarding the MF-related symptoms, 43.75% (n =7) of patients reported some improvement, 37.5% (n =6) showed no changes, whereas 18.75% (n =3) of the population complained of worsening. Gastrointestinal toxicity was the most frequent adverse effect of the drug, while 31% of patients died. CONCLUSION Our observations showed that in MF patients who have failed to ruxolitinib, the therapeutic value from fedratinib may be modest especially when exposure time to ruxolitinib was more than 12 months. We may hypothesize that earlier switching from ruxolitinib to fedratinib may yield a better result.