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Outcomes of Fedratinib in Routine Treatment of Ruxolitinib-Resistant or -Refractory Patients with Primary and
Adrian Duek1, Alexandra Tzinman1, Kira Maziuk1
1Samson Assuta Ashdod Public Hospital, Ashdod, Israel.
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 USA 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 15.5 cm below the costal margin (range: 4-22 cm). After 3 months the median spleen size was 13 cm below the costal margin (range: 2-21 cm). Only 2 patients showed minimal improvement after 6 months, while 3 patients progressed, and 2 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. Early switching from ruxolitinib to fedratinib may yield a better result.
Insights
Fedratinib showed modest benefits for myelofibrosis patients after ruxolitinib failure, particularly when ruxolitinib was used for over 12 months. Early switching may improve outcomes in myelofibrosis (MF) treatment.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Fedratinib, a JAK2 inhibitor, is a potential therapy for myelofibrosis (MF) patients who have not responded to or cannot tolerate ruxolitinib.
- Real-world data on fedratinib efficacy after ruxolitinib failure is limited and potentially less conclusive than clinical trial results.
Purpose of the Study:
- To evaluate the real-world effectiveness of fedratinib in Israeli patients with MF who previously failed ruxolitinib.
- To analyze treatment patterns and clinical outcomes in this specific patient population.
Main Methods:
- Retrospective review of patient charts for adults diagnosed with MF.
- Inclusion criteria: initiation of fedratinib after discontinuing ruxolitinib.
- Descriptive analyses of patient characteristics, MF progression, and treatment outcomes.
Main Results:
- 16 patients were analyzed; 62.5% were female, median age 77 years.
- Spleen size reduction was minimal and did not improve significantly over 12 months.
- Symptom improvement was reported by 43.75%, while 31% of patients died; gastrointestinal toxicity was common.
Conclusions:
- Fedratinib offers modest therapeutic value for MF patients with prior ruxolitinib failure, especially after prolonged ruxolitinib use (>12 months).
- Consideration of earlier switching from ruxolitinib to fedratinib might lead to better clinical outcomes.
