FREEDOM2 Trial Shows Fedratinib’s Efficacy and Safety in Myelofibrosis
The FREEDOM2 study demonstrates that fedratinib is an effective second-line treatment for myelofibrosis after ruxolitinib failure or intolerance.
Primary myelofibrosis cells in blood flow: © LASZLO - stock.adobe.com
When given as a second-line JAK inhibitor option in patients with myelofibrosis, fedratinib (Inrebic) showed its effectiveness in achieving spleen volume reduction (SVR) while highlighting strategies for managing gastrointestinal adverse effects (AEs) and thiamine deficiency, according to findings from the FREEDOM2 study (NCT03952039).1
The FREEDOM2 study, a multicenter, open-label, randomized controlled trial, involved 316 patients with intermediate-2 or high-risk myelofibrosis who were either relapsed, refractory, or intolerant to ruxolitinib (Jakafi).2 The median follow-up for survival at the data cutoff on December 27, 2022, was 64.5 weeks (IQR, 37.9-104.9). The primary end point was the proportion of patients achieving an SVR of at least 35% (SVR35) at the end of cycle 6.
Results from the study demonstrated a significant difference in SVR35 between the fedratinib and best available therapy (BAT) groups, with 36% of patients in the fedratinib group achieving the primary end point compared with only 6% in the BAT group (30% difference; 95% CI 20%-39%; 1-sided P <.0001).1
“Findings from FREEDOM2 support fedratinib as a second-line Janus kinase inhibitor option to reduce spleen size after ruxolitinib failure or intolerance in patients with myelofibrosis,” wrote study authors in findings published in The Lancet Hematology.
Of the 316 patients screened, 201 were randomly assigned to receive either fedratinib (n = 134) or BAT (n = 67), with 46 patients from the BAT group subsequently crossing over to receive fedratinib. The study was conducted between September 9, 2019, and June 24, 2022.
During the first 6 cycles, 40% of patients in the fedratinib group experienced grade 3 or greater treatment-related AEs vs 12% in the BAT group. The most common AEs included anemia (9% in the fedratinib arm vs 9% in the BAT arm) and thrombocytopenia (12% vs 3%). Additionally, there was 1 reported case of acute kidney injury suspected to be related to fedratinib.
Gastrointestinal AEs were more frequent in the fedratinib group compared with in the BAT group. However, most of these AEs were grade 1 to 2 in severity and occurred primarily during the initial cycles. Notably, these gastrointestinal AEs were less frequent than those reported in previous clinical trials.
A total of 21% of patients in the fedratinib group had low thiamine levels at baseline, with only 1 additional case observed after the introduction of prophylactic thiamine supplementation. This indicates that proactive monitoring and supplementation may mitigate the risk of thiamine deficiency.
