A study presented as part of the ASH 2020 Annual Meeting found that use of fedratinib for 24 or more weeks was well-tolerated in patients with intermediate- or high-risk myelofibrosis (MF).
Fedratinib is an oral Janus kinase 2 inhibitor that is approved by the U.S. Food and Drug Administration for the treatment of adults with intermediate-2 or high-risk MF. Researchers used longer-term follow-up data from the phase I/II TED12015 and phase I TED12037 studies to assess the safety of the drug’s extended use.
These open-label, dose-finding and extension studies included patients with intermediate- or high-risk primary, post-polycythemia vera, or post-essential thrombocythemia MF. In the TED12037 dose-finding study, 59 patients received continuous fedratinib at doses ranging from 30 mg to 800 mg per day for up to six 28-day treatment cycles. The maximum tolerated dose was 680 mg/day. Patients (n=43; 73%) with stable disease, clinical improvement, or complete or partial remission after six cycles could enter the TED12015 extension study at the last fedratinib dose they received in the dose-finding study.
A total of 28 patients (47%) received more than 24 cycles of fedratinib across both studies.
In this long-term cohort, median age at study entry was 62.5 years (range, 43-82 years). Patients received fedratinib for a median of 46 cycles (range, 25-72 cycles), for a total of 100.6 patient-years of exposure.
The median average fedratinib dose per patient was 462 mg/day (range, 283-800 mg), and overall treatment compliance rate was 98% (range, 80-100%). Patients discontinued fedratinib due to investigator decision (n=10), treatment-related adverse events (AEs; n=5), study termination (n=5), and disease progression (n=4).
Treatment-related AEs were highest during treatment cycles one through six and generally decreased or remained stable in later cycles. The most common treatment-related AEs after more than 24 cycles of fedratinib were hematologic and gastrointestinal events. Grade 3/4 AEs included thrombocytopenia, anemia, neutropenia, and pneumonia.
Few patients experienced late-emerging cardiac events or severe/opportunistic infections. One grade 1 case of congestive cardiac failure occurred during cycle seven. Four patients experienced five pneumonia events, all of which were grade 3 or 4; two events were considered possibly related to treatment. Three grade 3/4 serious neurologic AEs were reported, including post-herpetic neuralgia (n=2) and cerebrovascular accident (n=1).
“Although limited to a small patient population, these findings provide valuable information to guide clinical practice for pts who require long-term therapy,” the researchers concluded.