Dr. Harrison, of the Guy’s and St. Thomas’ NHS Foundation Trust, spoke about the FREEDOM2 study presented at the 65th American Society of Hematology Annual Meeting & Exposition.
FREEDOM2 is a phase III, randomized trial of the oral Janus kinase inhibitor fedratinib versus best available therapy as a second-line treatment for patients with myelofibrosis previously treated with ruxolitinib. The primary endpoint was a 35% reduction of spleen volume (SVR 35) at the end of cycle six.
“The vast majority of patients treated with fedratinib enjoyed a spleen volume reduction of some sort,” Dr. Harrison said.
SVR 35 was seen in 48 of 134 (36%) patients receiving fedratinib at the end of cycle six, compared with four (6%) patients receiving best available therapy. Meanwhile, the total symptom score was 34.1% for fedratinib and 16.9% for the control arm.
“A number of safety procedures were implemented in the study, which are important because they give us a readout of how well tolerated fedratinib is in this setting,” Dr. Harrison emphasized. These safety procedures include controlling gastrointestinal symptoms using antiemetic and antidiarrheal agents, as well as the monitoring of thiamine due to concerns about Wernicke encephalopathy.
According to Dr. Harrison, no grade 4 gastrointestinal toxicity was observed, and only one patient experienced grade 3 diarrhea or nausea.
“What’s also important is, ‘how do we use fedratinib in a way that patients can stay on it?’” Dr. Harrison noted. “Interestingly, this study tells us something about thiamine and thiamine deficiency.”
A total of 21% of patients in the fedratinib arm had a low thiamine level, compared with 5% of patients in the control arm.
“This is something we should take note of in routine clinical care,” Dr. Harrison said. “All in all, these results show very strong and superior SVR and symptom responses and a potent clinical benefit.”